12827833 XXBIX6VT 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22CHS3Y6QA%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Sollier%20et%20al.%22%2C%22parsedDate%22%3A%222024-01-04%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ESollier%2C%20J.%2C%20Basler%2C%20M.%2C%20Broz%2C%20P.%2C%20Dittrich%2C%20P.%20S.%2C%20Drescher%2C%20K.%2C%20Egli%2C%20A.%2C%20Harms%2C%20A.%2C%20Hierlemann%2C%20A.%2C%20Hiller%2C%20S.%2C%20King%2C%20C.%20G.%2C%20McKinney%2C%20J.%20D.%2C%20Moran-Gilad%2C%20J.%2C%20Neher%2C%20R.%20A.%2C%20Page%2C%20M.%20G.%20P.%2C%20Panke%2C%20S.%2C%20Persat%2C%20A.%2C%20Picotti%2C%20P.%2C%20Rentsch%2C%20K.%20M.%2C%20Rivera-Fuentes%2C%20P.%2C%20%5Cu2026%20Dehio%2C%20C.%20%282024%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41564-023-01566-w%27%3ERevitalizing%20antibiotic%20discovery%20and%20development%20through%20in%20vitro%20modelling%20of%20in-patient%20conditions%3C%5C%2Fa%3E.%20%3Ci%3ENature%20Microbiology%3C%5C%2Fi%3E%2C%20%3Ci%3E9%3C%5C%2Fi%3E%281%29%2C%201%5Cu20133.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41564-023-01566-w%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Revitalizing%20antibiotic%20discovery%20and%20development%20through%20in%20vitro%20modelling%20of%20in-patient%20conditions%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julie%22%2C%22lastName%22%3A%22Sollier%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Marek%22%2C%22lastName%22%3A%22Basler%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Petr%22%2C%22lastName%22%3A%22Broz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Petra%20S.%22%2C%22lastName%22%3A%22Dittrich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Knut%22%2C%22lastName%22%3A%22Drescher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Adrian%22%2C%22lastName%22%3A%22Egli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexander%22%2C%22lastName%22%3A%22Harms%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andreas%22%2C%22lastName%22%3A%22Hierlemann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sebastian%22%2C%22lastName%22%3A%22Hiller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Carolyn%20G.%22%2C%22lastName%22%3A%22King%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20D.%22%2C%22lastName%22%3A%22McKinney%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jacob%22%2C%22lastName%22%3A%22Moran-Gilad%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Richard%20A.%22%2C%22lastName%22%3A%22Neher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Malcolm%20G.%20P.%22%2C%22lastName%22%3A%22Page%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sven%22%2C%22lastName%22%3A%22Panke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexandre%22%2C%22lastName%22%3A%22Persat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paola%22%2C%22lastName%22%3A%22Picotti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Katharina%20M.%22%2C%22lastName%22%3A%22Rentsch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pablo%22%2C%22lastName%22%3A%22Rivera-Fuentes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daiana%22%2C%22lastName%22%3A%22Stolz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sarah%22%2C%22lastName%22%3A%22Tschudin-Sutter%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christian%22%2C%22lastName%22%3A%22Van%20Delden%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Erik%22%2C%22lastName%22%3A%22Van%20Nimwegen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jan-Willem%22%2C%22lastName%22%3A%22Veening%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Annelies%20S.%22%2C%22lastName%22%3A%22Zinkernagel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nina%22%2C%22lastName%22%3A%22Khanna%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Dirk%22%2C%22lastName%22%3A%22Bumann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Urs%22%2C%22lastName%22%3A%22Jenal%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christoph%22%2C%22lastName%22%3A%22Dehio%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222024-01-04%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41564-023-01566-w%22%2C%22ISSN%22%3A%222058-5276%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41564-023-01566-w%22%2C%22collections%22%3A%5B%22XXBIX6VT%22%5D%2C%22dateModified%22%3A%222024-04-30T09%3A11%3A31Z%22%7D%7D%5D%7DSollier, J., Basler, M., Broz, P., Dittrich, P. S., Drescher, K., Egli, A., Harms, A., Hierlemann, A., Hiller, S., King, C. G., McKinney, J. D., Moran-Gilad, J., Neher, R. A., Page, M. G. P., Panke, S., Persat, A., Picotti, P., Rentsch, K. M., Rivera-Fuentes, P., … Dehio, C. (2024). Revitalizing antibiotic discovery and development through in vitro modelling of in-patient conditions. Nature Microbiology, 9(1), 1–3. https://doi.org/10.1038/s41564-023-01566-w
12827833 AH528MCN 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%226Q42NFJI%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Gomez%20Solsona%20et%20al.%22%2C%22parsedDate%22%3A%222023-12-26%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EGomez%20Solsona%2C%20B.%2C%20Horn%2C%20H.%2C%20Schmitt%2C%20A.%2C%20Xu%2C%20W.%2C%20Bucher%2C%20P.%2C%20Heinrich%2C%20A.%2C%20Kalmbach%2C%20S.%2C%20Kreienkamp%2C%20N.%2C%20Franke%2C%20M.%2C%20Wimmers%2C%20F.%2C%20Schuhknecht%2C%20L.%2C%20Rosenwald%2C%20A.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Ott%2C%20G.%2C%20Lenz%2C%20G.%2C%20Schulze-Osthoff%2C%20K.%2C%20%26%20Hailfinger%2C%20S.%20%282023%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fashpublications.org%5C%2Fbloodadvances%5C%2Farticle%5C%2F7%5C%2F24%5C%2F7433%5C%2F498650%5C%2FInhibition-of-glutaminase-1-in-DLBCL-potentiates%27%3EInhibition%20of%20glutaminase-1%20in%20DLBCL%20potentiates%20venetoclax-induced%20antitumor%20activity%20by%20promoting%20oxidative%20stress%3C%5C%2Fa%3E.%20%3Ci%3EBlood%20Advances%3C%5C%2Fi%3E%2C%20%3Ci%3E7%3C%5C%2Fi%3E%2824%29%2C%207433%5Cu20137444.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1182%5C%2Fbloodadvances.2023010964%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Inhibition%20of%20glutaminase-1%20in%20DLBCL%20potentiates%20venetoclax-induced%20antitumor%20activity%20by%20promoting%20oxidative%20stress%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Beatriz%22%2C%22lastName%22%3A%22Gomez%20Solsona%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Heike%22%2C%22lastName%22%3A%22Horn%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anja%22%2C%22lastName%22%3A%22Schmitt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wendan%22%2C%22lastName%22%3A%22Xu%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Philip%22%2C%22lastName%22%3A%22Bucher%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Aylin%22%2C%22lastName%22%3A%22Heinrich%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sabrina%22%2C%22lastName%22%3A%22Kalmbach%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nina%22%2C%22lastName%22%3A%22Kreienkamp%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maik%22%2C%22lastName%22%3A%22Franke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Florian%22%2C%22lastName%22%3A%22Wimmers%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laurentz%22%2C%22lastName%22%3A%22Schuhknecht%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andreas%22%2C%22lastName%22%3A%22Rosenwald%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22German%22%2C%22lastName%22%3A%22Ott%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Georg%22%2C%22lastName%22%3A%22Lenz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Klaus%22%2C%22lastName%22%3A%22Schulze-Osthoff%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stephan%22%2C%22lastName%22%3A%22Hailfinger%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Diffuse%20large%20B-cell%20lymphoma%20%28DLBCL%29%20is%20the%20most%20common%20lymphoma%20in%20adults%2C%20but%20first-line%20immunochemotherapy%20fails%20to%20produce%20a%20durable%20response%20in%20about%20one-third%20of%20the%20patients.%20Because%20tumor%20cells%20often%20reprogram%20their%20metabolism%2C%20we%20investigated%20the%20importance%20of%20glutaminolysis%2C%20a%20pathway%20converting%20glutamine%20to%20generate%20energy%20and%20various%20metabolites%2C%20for%20the%20growth%20of%20DLBCL%20cells.%20Glutaminase-1%20%28GLS1%29%20expression%20was%20robustly%20detected%20in%20DLBCL%20biopsy%20samples%20and%20cell%20lines.%20Both%20pharmacological%20inhibition%20and%20genetic%20knockdown%20of%20GLS1%20induced%20cell%20death%20in%20DLBCL%20cells%20regardless%20of%20their%20subtype%20classification%2C%20whereas%20primary%20B%20cells%20remained%20unaffected.%20Interestingly%2C%20GLS1%20inhibition%20resulted%20not%20only%20in%20reduced%20levels%20of%20intermediates%20of%20the%20tricarboxylic%20acid%20cycle%20but%20also%20in%20a%20strong%20mitochondrial%20accumulation%20of%20reactive%20oxygen%20species.%20Supplementation%20of%20DLBCL%20cells%20with%20%5Cu03b1-ketoglutarate%20or%20with%20the%20antioxidant%20%5Cu03b1-tocopherol%20mitigated%20oxidative%20stress%20and%20abrogated%20cell%20death%20upon%20GLS1%20inhibition%2C%20indicating%20an%20essential%20role%20of%20glutaminolysis%20in%20the%20protection%20from%20oxidative%20stress.%20Furthermore%2C%20the%20combination%20of%20the%20GLS1%20inhibitor%20CB-839%20with%20the%20therapeutic%20BCL2%20inhibitor%20ABT-199%20not%20only%20induced%20massive%20reactive%20oxygen%20species%20%28ROS%29%20production%20but%20also%20exhibited%20highly%20synergistic%20cytotoxicity%2C%20suggesting%20that%20simultaneous%20targeting%20of%20GLS1%20and%20BCL2%20could%20represent%20a%20novel%20therapeutic%20strategy%20for%20patients%20with%20DLBCL.%22%2C%22date%22%3A%222023-12-26%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1182%5C%2Fbloodadvances.2023010964%22%2C%22ISSN%22%3A%222473-9529%2C%202473-9537%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fashpublications.org%5C%2Fbloodadvances%5C%2Farticle%5C%2F7%5C%2F24%5C%2F7433%5C%2F498650%5C%2FInhibition-of-glutaminase-1-in-DLBCL-potentiates%22%2C%22collections%22%3A%5B%22AH528MCN%22%5D%2C%22dateModified%22%3A%222024-05-02T12%3A06%3A37Z%22%7D%7D%2C%7B%22key%22%3A%2259MAV9LB%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Schmitt%20et%20al.%22%2C%22parsedDate%22%3A%222023-09-28%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ESchmitt%2C%20A.%2C%20Grimm%2C%20M.%2C%20Kreienkamp%2C%20N.%2C%20Junge%2C%20H.%2C%20Labisch%2C%20J.%2C%20Schuhknecht%2C%20L.%2C%20Sch%5Cu00f6nfeld%2C%20C.%2C%20G%5Cu00f6rsch%2C%20E.%2C%20Tibello%2C%20A.%2C%20Menck%2C%20K.%2C%20Bleckmann%2C%20A.%2C%20Lengerke%2C%20C.%2C%20Rosenbauer%2C%20F.%2C%20Grau%2C%20M.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Schulze-Osthoff%2C%20K.%2C%20Klener%2C%20P.%2C%20Dolnikova%2C%20A.%2C%20Lenz%2C%20G.%2C%20%26%20Hailfinger%2C%20S.%20%282023%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fashpublications.org%5C%2Fblood%5C%2Farticle%5C%2F142%5C%2F13%5C%2F1143%5C%2F496263%5C%2FBRD4-inhibition-sensitizes-diffuse-large-B-cell%27%3EBRD4%20inhibition%20sensitizes%20diffuse%20large%20B-cell%20lymphoma%20cells%20to%20ferroptosis%3C%5C%2Fa%3E.%20%3Ci%3EBlood%3C%5C%2Fi%3E%2C%20%3Ci%3E142%3C%5C%2Fi%3E%2813%29%2C%201143%5Cu20131155.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1182%5C%2Fblood.2022019274%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22BRD4%20inhibition%20sensitizes%20diffuse%20large%20B-cell%20lymphoma%20cells%20to%20ferroptosis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Anja%22%2C%22lastName%22%3A%22Schmitt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Melanie%22%2C%22lastName%22%3A%22Grimm%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nina%22%2C%22lastName%22%3A%22Kreienkamp%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hannah%22%2C%22lastName%22%3A%22Junge%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jan%22%2C%22lastName%22%3A%22Labisch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laurentz%22%2C%22lastName%22%3A%22Schuhknecht%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Caroline%22%2C%22lastName%22%3A%22Sch%5Cu00f6nfeld%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Elsa%22%2C%22lastName%22%3A%22G%5Cu00f6rsch%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alessia%22%2C%22lastName%22%3A%22Tibello%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kerstin%22%2C%22lastName%22%3A%22Menck%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Annalen%22%2C%22lastName%22%3A%22Bleckmann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudia%22%2C%22lastName%22%3A%22Lengerke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Frank%22%2C%22lastName%22%3A%22Rosenbauer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%22%2C%22lastName%22%3A%22Grau%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Klaus%22%2C%22lastName%22%3A%22Schulze-Osthoff%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pavel%22%2C%22lastName%22%3A%22Klener%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexandra%22%2C%22lastName%22%3A%22Dolnikova%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Georg%22%2C%22lastName%22%3A%22Lenz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stephan%22%2C%22lastName%22%3A%22Hailfinger%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Diffuse%20large%20B-cell%20lymphoma%20%28DLBCL%29%2C%20the%20most%20common%20form%20of%20non-Hodgkin%20lymphoma%2C%20is%20characterized%20by%20an%20aggressive%20clinical%20course.%20In%20approximately%20one-third%20of%20patients%20with%20DLBCL%2C%20first-line%20multiagent%20immunochemotherapy%20fails%20to%20produce%20a%20durable%20response.%20Molecular%20heterogeneity%20and%20apoptosis%20resistance%20pose%20major%20therapeutic%20challenges%20in%20DLBCL%20treatment.%20To%20circumvent%20apoptosis%20resistance%2C%20the%20induction%20of%20ferroptosis%20might%20represent%20a%20promising%20strategy%20for%20lymphoma%20therapy.%20In%20this%20study%2C%20a%20compound%20library%2C%20targeting%20epigenetic%20modulators%2C%20was%20screened%20to%20identify%20ferroptosis-sensitizing%20drugs.%20Strikingly%2C%20bromodomain%20and%20extra-terminal%20domain%20%28BET%29%20inhibitors%20sensitized%20cells%20of%20the%20germinal%20center%20B-cell%5Cu2013like%20%28GCB%29%20subtype%20of%20DLBCL%20to%20ferroptosis%20induction%20and%20the%20combination%20of%20BET%20inhibitors%20with%20ferroptosis%20inducers%2C%20such%20as%20dimethyl%20fumarate%20or%20RSL3%2C%20synergized%20in%20the%20killing%20of%20DLBCL%20cells%20in%5Cu00a0vitro%20and%20in%5Cu00a0vivo.%20On%20the%20molecular%20level%2C%20the%20BET%20protein%20BRD4%20was%20found%20to%20be%20an%20essential%20regulator%20of%20ferroptosis%20suppressor%20protein%201%20expression%20and%20thus%20to%20protect%20GCB-DLBCL%20cells%20from%20ferroptosis.%20Collectively%2C%20we%20identified%20and%20characterized%20BRD4%20as%20an%20important%20player%20in%20ferroptosis%20suppression%20in%20GCB-DLBCL%20and%20provide%20a%20rationale%20for%20the%20combination%20of%20BET%20inhibitors%20with%20ferroptosis-inducing%20agents%20as%20a%20novel%20therapeutic%20approach%20for%20DLBCL%20treatment.%22%2C%22date%22%3A%222023-09-28%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1182%5C%2Fblood.2022019274%22%2C%22ISSN%22%3A%220006-4971%2C%201528-0020%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fashpublications.org%5C%2Fblood%5C%2Farticle%5C%2F142%5C%2F13%5C%2F1143%5C%2F496263%5C%2FBRD4-inhibition-sensitizes-diffuse-large-B-cell%22%2C%22collections%22%3A%5B%22AH528MCN%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A46%3A10Z%22%7D%7D%5D%7DGomez Solsona, B., Horn, H., Schmitt, A., Xu, W., Bucher, P., Heinrich, A., Kalmbach, S., Kreienkamp, N., Franke, M., Wimmers, F., Schuhknecht, L., Rosenwald, A., Zampieri, M., Ott, G., Lenz, G., Schulze-Osthoff, K., & Hailfinger, S. (2023). Inhibition of glutaminase-1 in DLBCL potentiates venetoclax-induced antitumor activity by promoting oxidative stress. Blood Advances, 7(24), 7433–7444. https://doi.org/10.1182/bloodadvances.2023010964Schmitt, A., Grimm, M., Kreienkamp, N., Junge, H., Labisch, J., Schuhknecht, L., Schönfeld, C., Görsch, E., Tibello, A., Menck, K., Bleckmann, A., Lengerke, C., Rosenbauer, F., Grau, M., Zampieri, M., Schulze-Osthoff, K., Klener, P., Dolnikova, A., Lenz, G., & Hailfinger, S. (2023). BRD4 inhibition sensitizes diffuse large B-cell lymphoma cells to ferroptosis. Blood, 142(13), 1143–1155. https://doi.org/10.1182/blood.2022019274
12827833 2JDWCR54 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%226EDKKC77%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ortmayr%20and%20Zampieri%22%2C%22parsedDate%22%3A%222022%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EOrtmayr%2C%20K.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282022%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.embopress.org%5C%2Fdoi%5C%2F10.15252%5C%2Fmsb.202110716%27%3ESorting%5Cu2010free%20metabolic%20profiling%20uncovers%20the%20vulnerability%20of%20fatty%20acid%20%5Cu03b2%5Cu2010oxidation%20in%20%3Ci%3Ein%20vitro%3C%5C%2Fi%3E%20quiescence%20models%3C%5C%2Fa%3E.%20%3Ci%3EMolecular%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%289%29%2C%20e10716.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.15252%5C%2Fmsb.202110716%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Sorting%5Cu2010free%20metabolic%20profiling%20uncovers%20the%20vulnerability%20of%20fatty%20acid%20%5Cu03b2%5Cu2010oxidation%20in%20%3Ci%3Ein%20vitro%3C%5C%2Fi%3E%20quiescence%20models%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karin%22%2C%22lastName%22%3A%22Ortmayr%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2209%5C%2F2022%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.15252%5C%2Fmsb.202110716%22%2C%22ISSN%22%3A%221744-4292%2C%201744-4292%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.embopress.org%5C%2Fdoi%5C%2F10.15252%5C%2Fmsb.202110716%22%2C%22collections%22%3A%5B%222JDWCR54%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A48%3A18Z%22%7D%7D%2C%7B%22key%22%3A%22CEAYR7XU%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ortmayr%20et%20al.%22%2C%22parsedDate%22%3A%222022%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EOrtmayr%2C%20K.%2C%20De%20La%20Cruz%20Moreno%2C%20R.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282022%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41589-022-01040-4%27%3EExpanding%20the%20search%20for%20small-molecule%20antibacterials%20by%20multidimensional%20profiling%3C%5C%2Fa%3E.%20%3Ci%3ENature%20Chemical%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%286%29%2C%20584%5Cu2013595.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41589-022-01040-4%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Expanding%20the%20search%20for%20small-molecule%20antibacterials%20by%20multidimensional%20profiling%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karin%22%2C%22lastName%22%3A%22Ortmayr%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Roberto%22%2C%22lastName%22%3A%22De%20La%20Cruz%20Moreno%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2206%5C%2F2022%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41589-022-01040-4%22%2C%22ISSN%22%3A%221552-4450%2C%201552-4469%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41589-022-01040-4%22%2C%22collections%22%3A%5B%222JDWCR54%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A47%3A55Z%22%7D%7D%2C%7B%22key%22%3A%2298CPGSBM%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Anglada-Girotto%20et%20al.%22%2C%22parsedDate%22%3A%222022%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAnglada-Girotto%2C%20M.%2C%20Handschin%2C%20G.%2C%20Ortmayr%2C%20K.%2C%20Campos%2C%20A.%20I.%2C%20Gillet%2C%20L.%2C%20Manfredi%2C%20P.%2C%20Mulholland%2C%20C.%20V.%2C%20Berney%2C%20M.%2C%20Jenal%2C%20U.%2C%20Picotti%2C%20P.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282022%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41589-022-00970-3%27%3ECombining%20CRISPRi%20and%20metabolomics%20for%20functional%20annotation%20of%20compound%20libraries%3C%5C%2Fa%3E.%20%3Ci%3ENature%20Chemical%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E18%3C%5C%2Fi%3E%285%29%2C%20482%5Cu2013491.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41589-022-00970-3%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Combining%20CRISPRi%20and%20metabolomics%20for%20functional%20annotation%20of%20compound%20libraries%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Miquel%22%2C%22lastName%22%3A%22Anglada-Girotto%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Gabriel%22%2C%22lastName%22%3A%22Handschin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karin%22%2C%22lastName%22%3A%22Ortmayr%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Adrian%20I.%22%2C%22lastName%22%3A%22Campos%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ludovic%22%2C%22lastName%22%3A%22Gillet%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pablo%22%2C%22lastName%22%3A%22Manfredi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claire%20V.%22%2C%22lastName%22%3A%22Mulholland%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%22%2C%22lastName%22%3A%22Berney%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Urs%22%2C%22lastName%22%3A%22Jenal%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paola%22%2C%22lastName%22%3A%22Picotti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2205%5C%2F2022%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41589-022-00970-3%22%2C%22ISSN%22%3A%221552-4450%2C%201552-4469%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41589-022-00970-3%22%2C%22collections%22%3A%5B%222JDWCR54%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A47%3A05Z%22%7D%7D%5D%7DOrtmayr, K., & Zampieri, M. (2022). Sorting‐free metabolic profiling uncovers the vulnerability of fatty acid β‐oxidation in in vitro quiescence models. Molecular Systems Biology, 18(9), e10716. https://doi.org/10.15252/msb.202110716Ortmayr, K., De La Cruz Moreno, R., & Zampieri, M. (2022). Expanding the search for small-molecule antibacterials by multidimensional profiling. Nature Chemical Biology, 18(6), 584–595. https://doi.org/10.1038/s41589-022-01040-4Anglada-Girotto, M., Handschin, G., Ortmayr, K., Campos, A. I., Gillet, L., Manfredi, P., Mulholland, C. V., Berney, M., Jenal, U., Picotti, P., & Zampieri, M. (2022). Combining CRISPRi and metabolomics for functional annotation of compound libraries. Nature Chemical Biology, 18(5), 482–491. https://doi.org/10.1038/s41589-022-00970-3
12827833 7MNEEJI6 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22NW65KHTF%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%22%2C%22parsedDate%22%3A%222021-02-19%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282021%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscience.abf7922%27%3EThe%20genetic%20underground%20of%20antibiotic%20resistance%3C%5C%2Fa%3E.%20%3Ci%3EScience%3C%5C%2Fi%3E%2C%20%3Ci%3E371%3C%5C%2Fi%3E%286531%29%2C%20783%5Cu2013784.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscience.abf7922%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22The%20genetic%20underground%20of%20antibiotic%20resistance%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22The%20silent%20role%20and%20clinical%20relevance%20of%20metabolic%20mutations%20in%20antibiotic%20resistance%20begin%20to%20be%20unravelled%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Metabolism%20has%20mostly%20been%20studied%20for%20its%20role%20in%20providing%20building%20blocks%20and%20energy%20to%20sustain%20cell%20duplication.%20Previously%20unexplored%20roles%20of%20metabolism%20in%20signaling%20and%20regulation%20have%20now%20been%20unveiled.%20Mounting%20evidence%20suggests%20a%20fundamental%20role%20of%20microbial%20metabolism%20in%20mediating%20the%20short-term%20%28%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%201%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2C%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%202%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29%20and%20long-term%20responses%20to%20antimicrobial%20agents%20%28%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%203%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29%2C%20opening%20possibilities%20for%20combination%20therapies%20that%20could%20hamper%20the%20evolution%20of%20antibiotic%20resistance%20%28%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%204%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cu2013%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%206%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29.%20Given%20their%20impact%20on%20bacterial%20growth%2C%20indirect%20effects%20of%20antibiotic%20treatment%20on%20metabolism%20were%20to%20be%20expected.%20But%20there%20are%20also%20common%20and%20drug-specific%20metabolic%20changes%20that%20are%20independent%20from%20growth%20inhibition%20and%20can%20play%20an%20important%20role%20in%20antibiotic%20lethality%20%28%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%201%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2C%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%205%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2C%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%206%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29.%20If%20metabolism%20plays%20a%20key%20role%20in%20mediating%20antibiotic%20response%20and%20drug%20toxicity%2C%20does%20metabolism%20have%20a%20role%20in%20antibiotic%20resistance%3F%20On%20page%20799%20of%20this%20issue%2C%20Lopatkin%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20et%20al.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%28%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%207%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29%20reveal%20the%20interplay%20between%20metabolism%20and%20antibiotic%20resistance%20in%20clinically%20relevant%20pathogens.%22%2C%22date%22%3A%222021-02-19%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1126%5C%2Fscience.abf7922%22%2C%22ISSN%22%3A%220036-8075%2C%201095-9203%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscience.abf7922%22%2C%22collections%22%3A%5B%227MNEEJI6%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A43%3A29Z%22%7D%7D%2C%7B%22key%22%3A%22ZJPIKZ3C%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Fuentes%20et%20al.%22%2C%22parsedDate%22%3A%222021-05-28%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EFuentes%2C%20D.%20A.%20F.%2C%20Manfredi%2C%20P.%2C%20Jenal%2C%20U.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282021%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-021-23522-0%27%3EPareto%20optimality%20between%20growth-rate%20and%20lag-time%20couples%20metabolic%20noise%20to%20phenotypic%20heterogeneity%20in%20Escherichia%20coli%3C%5C%2Fa%3E.%20%3Ci%3ENature%20Communications%3C%5C%2Fi%3E%2C%20%3Ci%3E12%3C%5C%2Fi%3E%281%29%2C%203204.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-021-23522-0%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Pareto%20optimality%20between%20growth-rate%20and%20lag-time%20couples%20metabolic%20noise%20to%20phenotypic%20heterogeneity%20in%20Escherichia%20coli%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Diego%20Antonio%20Fernandez%22%2C%22lastName%22%3A%22Fuentes%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pablo%22%2C%22lastName%22%3A%22Manfredi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Urs%22%2C%22lastName%22%3A%22Jenal%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Despite%20mounting%20evidence%20that%20in%20clonal%20bacterial%20populations%2C%20phenotypic%20variability%20originates%20from%20stochasticity%20in%20gene%20expression%2C%20little%20is%20known%20about%20noise-shaping%20evolutionary%20forces%20and%20how%20expression%20noise%20translates%20to%20phenotypic%20differences.%20Here%20we%20developed%20a%20high-throughput%20assay%20that%20uses%20a%20redox-sensitive%20dye%20to%20couple%20growth%20of%20thousands%20of%20bacterial%20colonies%20to%20their%20respiratory%20activity%20and%20show%20that%20in%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Escherichia%20coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2C%20noisy%20regulation%20of%20lower%20glycolysis%20and%20citric%20acid%20cycle%20is%20responsible%20for%20large%20variations%20in%20respiratory%20metabolism.%20We%20found%20that%20these%20variations%20are%20Pareto%20optimal%20to%20maximization%20of%20growth%20rate%20and%20minimization%20of%20lag%20time%2C%20two%20objectives%20competing%20between%20fermentative%20and%20respiratory%20metabolism.%20Metabolome-based%20analysis%20revealed%20the%20role%20of%20respiratory%20metabolism%20in%20preventing%20the%20accumulation%20of%20toxic%20intermediates%20of%20branched%20chain%20amino%20acid%20biosynthesis%2C%20thereby%20supporting%20early%20onset%20of%20cell%20growth%20after%20carbon%20starvation.%20We%20propose%20that%20optimal%20metabolic%20tradeoffs%20play%20a%20key%20role%20in%20shaping%20and%20preserving%20phenotypic%20heterogeneity%20and%20adaptation%20to%20fluctuating%20environments.%22%2C%22date%22%3A%222021-05-28%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-021-23522-0%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-021-23522-0%22%2C%22collections%22%3A%5B%227MNEEJI6%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A42%3A46Z%22%7D%7D%2C%7B%22key%22%3A%22GZ62A9W2%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Trauner%20et%20al.%22%2C%22parsedDate%22%3A%222021-08-17%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ETrauner%2C%20A.%2C%20Banaei-Esfahani%2C%20A.%2C%20Gygli%2C%20S.%20M.%2C%20Warmer%2C%20P.%2C%20Feldmann%2C%20J.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Borrell%2C%20S.%2C%20Collins%2C%20B.%20C.%2C%20Beisel%2C%20C.%2C%20Aebersold%2C%20R.%2C%20%26%20Gagneux%2C%20S.%20%282021%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fjournals.asm.org%5C%2Fdoi%5C%2F10.1128%5C%2FAAC.00504-21%27%3EExpression%20Dysregulation%20as%20a%20Mediator%20of%20Fitness%20Costs%20in%20Antibiotic%20Resistance%3C%5C%2Fa%3E.%20%3Ci%3EAntimicrobial%20Agents%20and%20Chemotherapy%3C%5C%2Fi%3E%2C%20%3Ci%3E65%3C%5C%2Fi%3E%289%29%2C%20e00504-21.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1128%5C%2FAAC.00504-21%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Expression%20Dysregulation%20as%20a%20Mediator%20of%20Fitness%20Costs%20in%20Antibiotic%20Resistance%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrej%22%2C%22lastName%22%3A%22Trauner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Amir%22%2C%22lastName%22%3A%22Banaei-Esfahani%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sebastian%20M.%22%2C%22lastName%22%3A%22Gygli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Philipp%22%2C%22lastName%22%3A%22Warmer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julia%22%2C%22lastName%22%3A%22Feldmann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sonia%22%2C%22lastName%22%3A%22Borrell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ben%20C.%22%2C%22lastName%22%3A%22Collins%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christian%22%2C%22lastName%22%3A%22Beisel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ruedi%22%2C%22lastName%22%3A%22Aebersold%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sebastien%22%2C%22lastName%22%3A%22Gagneux%22%7D%5D%2C%22abstractNote%22%3A%22Antimicrobial%20resistance%20%28AMR%29%20poses%20a%20threat%20to%20global%20health%20and%20the%20economy.%20Rifampicin-resistant%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20tuberculosis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20accounts%20for%20a%20third%20of%20the%20global%20AMR%20burden.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20ABSTRACT%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Antimicrobial%20resistance%20%28AMR%29%20poses%20a%20threat%20to%20global%20health%20and%20the%20economy.%20Rifampicin-resistant%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20tuberculosis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20accounts%20for%20a%20third%20of%20the%20global%20AMR%20burden.%20Gaining%20the%20upper%20hand%20on%20AMR%20requires%20a%20deeper%20understanding%20of%20the%20physiology%20of%20resistance.%20AMR%20often%20results%20in%20a%20fitness%20cost%20in%20the%20absence%20of%20drug.%20Identifying%20the%20molecular%20mechanisms%20underpinning%20this%20cost%20could%20help%20strengthen%20future%20treatment%20regimens.%20Here%2C%20we%20used%20a%20collection%20of%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20M.%20tuberculosis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20strains%20that%20provide%20an%20evolutionary%20and%20phylogenetic%20snapshot%20of%20rifampicin%20resistance%20and%20subjected%20them%20to%20genome-wide%20transcriptomic%20and%20proteomic%20profiling%20to%20identify%20key%20perturbations%20of%20normal%20physiology.%20We%20found%20that%20the%20clinically%20most%20common%20rifampicin%20resistance-conferring%20mutation%2C%20RpoB%20Ser450Leu%2C%20imparts%20considerable%20gene%20expression%20changes%2C%20many%20of%20which%20are%20mitigated%20by%20the%20compensatory%20mutation%20in%20RpoC%20Leu516Pro.%20However%2C%20our%20data%20also%20provide%20evidence%20for%20pervasive%20epistasis%5Cu2014the%20same%20resistance%20mutation%20imposed%20a%20different%20fitness%20cost%20and%20functionally%20distinct%20changes%20to%20gene%20expression%20in%20genetically%20unrelated%20clinical%20strains.%20Finally%2C%20we%20report%20a%20likely%20posttranscriptional%20modulation%20of%20gene%20expression%20that%20is%20shared%20in%20most%20of%20the%20tested%20strains%20carrying%20RpoB%20Ser450Leu%2C%20resulting%20in%20an%20increased%20abundance%20of%20proteins%20involved%20in%20central%20carbon%20metabolism.%20These%20changes%20contribute%20to%20a%20more%20general%20trend%20in%20which%20the%20disruption%20of%20the%20composition%20of%20the%20proteome%20correlates%20with%20the%20fitness%20cost%20of%20the%20RpoB%20Ser450Leu%20mutation%20in%20different%20strains.%22%2C%22date%22%3A%222021-08-17%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1128%5C%2FAAC.00504-21%22%2C%22ISSN%22%3A%220066-4804%2C%201098-6596%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fjournals.asm.org%5C%2Fdoi%5C%2F10.1128%5C%2FAAC.00504-21%22%2C%22collections%22%3A%5B%227MNEEJI6%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A41%3A39Z%22%7D%7D%5D%7DZampieri, M. (2021). The genetic underground of antibiotic resistance. Science, 371(6531), 783–784. https://doi.org/10.1126/science.abf7922Fuentes, D. A. F., Manfredi, P., Jenal, U., & Zampieri, M. (2021). Pareto optimality between growth-rate and lag-time couples metabolic noise to phenotypic heterogeneity in Escherichia coli. Nature Communications, 12(1), 3204. https://doi.org/10.1038/s41467-021-23522-0Trauner, A., Banaei-Esfahani, A., Gygli, S. M., Warmer, P., Feldmann, J., Zampieri, M., Borrell, S., Collins, B. C., Beisel, C., Aebersold, R., & Gagneux, S. (2021). Expression Dysregulation as a Mediator of Fitness Costs in Antibiotic Resistance. Antimicrobial Agents and Chemotherapy, 65(9), e00504-21. https://doi.org/10.1128/AAC.00504-21
12827833 8IB48ZA3 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22GZPW99PT%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22%5Cu00d8y%5Cu00e5s%20et%20al.%22%2C%22parsedDate%22%3A%222020-04-14%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%5Cu00d8y%5Cu00e5s%2C%20O.%2C%20Borrell%2C%20S.%2C%20Trauner%2C%20A.%2C%20Zimmermann%2C%20M.%2C%20Feldmann%2C%20J.%2C%20Liphardt%2C%20T.%2C%20Gagneux%2C%20S.%2C%20Stelling%2C%20J.%2C%20Sauer%2C%20U.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282020%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fpnas.org%5C%2Fdoi%5C%2Ffull%5C%2F10.1073%5C%2Fpnas.1915551117%27%3EModel-based%20integration%20of%20genomics%20and%20metabolomics%20reveals%20SNP%20functionality%20in%20%3Ci%3EMycobacterium%20tuberculosis%3C%5C%2Fi%3E%3C%5C%2Fa%3E.%20%3Ci%3EProceedings%20of%20the%20National%20Academy%20of%20Sciences%3C%5C%2Fi%3E%2C%20%3Ci%3E117%3C%5C%2Fi%3E%2815%29%2C%208494%5Cu20138502.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1073%5C%2Fpnas.1915551117%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Model-based%20integration%20of%20genomics%20and%20metabolomics%20reveals%20SNP%20functionality%20in%20%3Ci%3EMycobacterium%20tuberculosis%3C%5C%2Fi%3E%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ove%22%2C%22lastName%22%3A%22%5Cu00d8y%5Cu00e5s%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sonia%22%2C%22lastName%22%3A%22Borrell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrej%22%2C%22lastName%22%3A%22Trauner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%22%2C%22lastName%22%3A%22Zimmermann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julia%22%2C%22lastName%22%3A%22Feldmann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%22%2C%22lastName%22%3A%22Liphardt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sebastien%22%2C%22lastName%22%3A%22Gagneux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22J%5Cu00f6rg%22%2C%22lastName%22%3A%22Stelling%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22Significance%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Because%20genetic%20diversity%20in%20the%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20tuberculosis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20complex%20%28MTBC%29%20is%20less%20pronounced%20than%20in%20other%20pathogens%2C%20the%20variable%20outcome%20of%20infection%20has%20been%20attributed%20mainly%20to%20host%20and%20environmental%20factors.%20Here%2C%20we%20reveal%20widely%20different%20metabolic%20phenotypes%20among%20MTBC%20members%2C%20suggesting%20that%20strain%20diversity%20may%20play%20an%20important%20role%20during%20infection.%20To%20unravel%20the%20genetic%20basis%20for%20metabolic%20diversity%2C%20we%20developed%20a%20approach%20that%20integrates%20metabolomic%20and%20genomic%20data%20for%2018%20MTBC%20clinical%20strains.%20Our%20approach%20allowed%20us%20to%20investigate%20the%20metabolic%20effect%20of%20rare%20genetic%20variants%20and%20to%20predict%20mutations%20that%20associate%20with%20strain-specific%20metabolic%20vulnerabilities%20and%20inherent%20baseline%20susceptibility%20to%20antibiotics.%20Our%20model-based%20approach%20is%20broadly%20applicable%20to%20many%20organisms%2C%20opening%20possibilities%20for%20identifying%20more%20selective%20treatment%20strategies.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Human%20tuberculosis%20is%20caused%20by%20members%20of%20the%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20tuberculosis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20complex%20%28MTBC%29%20that%20vary%20in%20virulence%20and%20transmissibility.%20While%20genome-wide%20association%20studies%20have%20uncovered%20several%20mutations%20conferring%20drug%20resistance%2C%20much%20less%20is%20known%20about%20the%20factors%20underlying%20other%20bacterial%20phenotypes.%20Variation%20in%20the%20outcome%20of%20tuberculosis%20infection%20and%20diseases%20has%20been%20attributed%20primarily%20to%20patient%20and%20environmental%20factors%2C%20but%20recent%20evidence%20indicates%20an%20additional%20role%20for%20the%20genetic%20diversity%20among%20MTBC%20clinical%20strains.%20Here%2C%20we%20used%20metabolomics%20to%20unravel%20the%20effect%20of%20genetic%20variation%20on%20the%20strain-specific%20metabolic%20adaptive%20capacity%20and%20vulnerability.%20To%20define%20the%20functionality%20of%20single-nucleotide%20polymorphisms%20%28SNPs%29%20systematically%2C%20we%20developed%20a%20constraint-based%20approach%20that%20integrates%20metabolomic%20and%20genomic%20data.%20Our%20model-based%20predictions%20correctly%20classify%20SNP%20effects%20in%20pyruvate%20kinase%20and%20suggest%20a%20genetic%20basis%20for%20strain-specific%20inherent%20baseline%20susceptibility%20to%20the%20antibiotic%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20para%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20-aminosalicylic%20acid.%20Our%20method%20is%20broadly%20applicable%20across%20microbial%20life%2C%20opening%20possibilities%20for%20the%20development%20of%20more%20selective%20treatment%20strategies.%22%2C%22date%22%3A%222020-04-14%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1073%5C%2Fpnas.1915551117%22%2C%22ISSN%22%3A%220027-8424%2C%201091-6490%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fpnas.org%5C%2Fdoi%5C%2Ffull%5C%2F10.1073%5C%2Fpnas.1915551117%22%2C%22collections%22%3A%5B%228IB48ZA3%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A44%3A38Z%22%7D%7D%5D%7DØyås, O., Borrell, S., Trauner, A., Zimmermann, M., Feldmann, J., Liphardt, T., Gagneux, S., Stelling, J., Sauer, U., & Zampieri, M. (2020). Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences, 117(15), 8494–8502. https://doi.org/10.1073/pnas.1915551117
12827833 FJ8BH6EC 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%222J4XVL6R%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Ortmayr%20et%20al.%22%2C%22parsedDate%22%3A%222019-04-23%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EOrtmayr%2C%20K.%2C%20Dubuis%2C%20S.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282019%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-019-09695-9%27%3EMetabolic%20profiling%20of%20cancer%20cells%20reveals%20genome-wide%20crosstalk%20between%20transcriptional%20regulators%20and%20metabolism%3C%5C%2Fa%3E.%20%3Ci%3ENature%20Communications%3C%5C%2Fi%3E%2C%20%3Ci%3E10%3C%5C%2Fi%3E%281%29%2C%201841.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-019-09695-9%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Metabolic%20profiling%20of%20cancer%20cells%20reveals%20genome-wide%20crosstalk%20between%20transcriptional%20regulators%20and%20metabolism%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karin%22%2C%22lastName%22%3A%22Ortmayr%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S%5Cu00e9bastien%22%2C%22lastName%22%3A%22Dubuis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Transcriptional%20reprogramming%20of%20cellular%20metabolism%20is%20a%20hallmark%20of%20cancer.%20However%2C%20systematic%20approaches%20to%20study%20the%20role%20of%20transcriptional%20regulators%20%28TRs%29%20in%20mediating%20cancer%20metabolic%20rewiring%20are%20missing.%20Here%2C%20we%20chart%20a%20genome-scale%20map%20of%20TR-metabolite%20associations%20in%20human%20cells%20using%20a%20combined%20computational-experimental%20framework%20for%20large-scale%20metabolic%20profiling%20of%20adherent%20cell%20lines.%20By%20integrating%20intracellular%20metabolic%20profiles%20of%2054%20cancer%20cell%20lines%20with%20transcriptomic%20and%20proteomic%20data%2C%20we%20unraveled%20a%20large%20space%20of%20associations%20between%20TRs%20and%20metabolic%20pathways.%20We%20found%20a%20global%20regulatory%20signature%20coordinating%20glucose-%20and%20one-carbon%20metabolism%2C%20suggesting%20that%20regulation%20of%20carbon%20metabolism%20in%20cancer%20may%20be%20more%20diverse%20and%20flexible%20than%20previously%20appreciated.%20Here%2C%20we%20demonstrate%20how%20this%20TR-metabolite%20map%20can%20serve%20as%20a%20resource%20to%20predict%20TRs%20potentially%20responsible%20for%20metabolic%20transformation%20in%20patient-derived%20tumor%20samples%2C%20opening%20new%20opportunities%20in%20understanding%20disease%20etiology%2C%20selecting%20therapeutic%20treatments%20and%20in%20designing%20modulators%20of%20cancer-related%20TRs.%22%2C%22date%22%3A%222019-04-23%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-019-09695-9%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-019-09695-9%22%2C%22collections%22%3A%5B%22FJ8BH6EC%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A48%3A52Z%22%7D%7D%2C%7B%22key%22%3A%22P9F68NPY%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Campos%20and%20Zampieri%22%2C%22parsedDate%22%3A%222019%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ECampos%2C%20A.%20I.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282019%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS1097276519302710%27%3EMetabolomics-Driven%20Exploration%20of%20the%20Chemical%20Drug%20Space%20to%20Predict%20Combination%20Antimicrobial%20Therapies%3C%5C%2Fa%3E.%20%3Ci%3EMolecular%20Cell%3C%5C%2Fi%3E%2C%20%3Ci%3E74%3C%5C%2Fi%3E%286%29%2C%201291-1303.e6.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.molcel.2019.04.001%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Metabolomics-Driven%20Exploration%20of%20the%20Chemical%20Drug%20Space%20to%20Predict%20Combination%20Antimicrobial%20Therapies%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Adrian%20I.%22%2C%22lastName%22%3A%22Campos%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2206%5C%2F2019%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.molcel.2019.04.001%22%2C%22ISSN%22%3A%2210972765%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS1097276519302710%22%2C%22collections%22%3A%5B%22FJ8BH6EC%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A45%3A44Z%22%7D%7D%2C%7B%22key%22%3A%22VKMNA6S7%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222019-07-26%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20H%5Cu00f6rl%2C%20M.%2C%20Hotz%2C%20F.%2C%20M%5Cu00fcller%2C%20N.%20F.%2C%20%26%20Sauer%2C%20U.%20%282019%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-019-11331-5%27%3ERegulatory%20mechanisms%20underlying%20coordination%20of%20amino%20acid%20and%20glucose%20catabolism%20in%20Escherichia%20coli%3C%5C%2Fa%3E.%20%3Ci%3ENature%20Communications%3C%5C%2Fi%3E%2C%20%3Ci%3E10%3C%5C%2Fi%3E%281%29%2C%203354.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41467-019-11331-5%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Regulatory%20mechanisms%20underlying%20coordination%20of%20amino%20acid%20and%20glucose%20catabolism%20in%20Escherichia%20coli%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Manuel%22%2C%22lastName%22%3A%22H%5Cu00f6rl%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Florian%22%2C%22lastName%22%3A%22Hotz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicola%20F.%22%2C%22lastName%22%3A%22M%5Cu00fcller%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20How%20microbes%20dynamically%20coordinate%20uptake%20and%20simultaneous%20utilization%20of%20nutrients%20in%20complex%20nutritional%20ecosystems%20is%20still%20an%20open%20question.%20Here%2C%20we%20develop%20a%20constraint-based%20modeling%20approach%20that%20exploits%20non-targeted%20exo-metabolomics%20data%20to%20unravel%20adaptive%20decision-making%20processes%20in%20dynamic%20nutritional%20environments.%20We%20thereby%20investigate%20metabolic%20adaptation%20of%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Escherichia%20coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20to%20continuously%20changing%20conditions%20during%20batch%20growth%20in%20complex%20medium.%20Unexpectedly%2C%20model-based%20analysis%20of%20time%20resolved%20exo-metabolome%20data%20revealed%20that%20fastest%20growth%20coincides%20with%20preferred%20catabolism%20of%20amino%20acids%2C%20which%2C%20in%20turn%2C%20reduces%20glucose%20uptake%20and%20increases%20acetate%20overflow.%20We%20show%20that%20high%20intracellular%20levels%20of%20the%20amino%20acid%20degradation%20metabolites%20pyruvate%20and%20oxaloacetate%20can%20directly%20inhibit%20the%20phosphotransferase%20system%20%28PTS%29%2C%20and%20reveal%20their%20functional%20role%20in%20mediating%20regulatory%20decisions%20for%20uptake%20and%20catabolism%20of%20alternative%20carbon%20sources.%20Overall%2C%20the%20proposed%20methodology%20expands%20the%20spectrum%20of%20possible%20applications%20of%20flux%20balance%20analysis%20to%20decipher%20metabolic%20adaptation%20mechanisms%20in%20naturally%20occurring%20habitats%20and%20diverse%20organisms.%22%2C%22date%22%3A%222019-07-26%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41467-019-11331-5%22%2C%22ISSN%22%3A%222041-1723%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs41467-019-11331-5%22%2C%22collections%22%3A%5B%22FJ8BH6EC%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A45%3A23Z%22%7D%7D%5D%7DOrtmayr, K., Dubuis, S., & Zampieri, M. (2019). Metabolic profiling of cancer cells reveals genome-wide crosstalk between transcriptional regulators and metabolism. Nature Communications, 10(1), 1841. https://doi.org/10.1038/s41467-019-09695-9Campos, A. I., & Zampieri, M. (2019). Metabolomics-Driven Exploration of the Chemical Drug Space to Predict Combination Antimicrobial Therapies. Molecular Cell, 74(6), 1291-1303.e6. https://doi.org/10.1016/j.molcel.2019.04.001Zampieri, M., Hörl, M., Hotz, F., Müller, N. F., & Sauer, U. (2019). Regulatory mechanisms underlying coordination of amino acid and glucose catabolism in Escherichia coli. Nature Communications, 10(1), 3354. https://doi.org/10.1038/s41467-019-11331-5
12827833 DMTSVRD2 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%229UNUSJJJ%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222018-02-21%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Szappanos%2C%20B.%2C%20Buchieri%2C%20M.%20V.%2C%20Trauner%2C%20A.%2C%20Piazza%2C%20I.%2C%20Picotti%2C%20P.%2C%20Gagneux%2C%20S.%2C%20Borrell%2C%20S.%2C%20Gicquel%2C%20B.%2C%20Lelievre%2C%20J.%2C%20Papp%2C%20B.%2C%20%26%20Sauer%2C%20U.%20%282018%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscitranslmed.aal3973%27%3EHigh-throughput%20metabolomic%20analysis%20predicts%20mode%20of%20action%20of%20uncharacterized%20antimicrobial%20compounds%3C%5C%2Fa%3E.%20%3Ci%3EScience%20Translational%20Medicine%3C%5C%2Fi%3E%2C%20%3Ci%3E10%3C%5C%2Fi%3E%28429%29%2C%20eaal3973.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscitranslmed.aal3973%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22High-throughput%20metabolomic%20analysis%20predicts%20mode%20of%20action%20of%20uncharacterized%20antimicrobial%20compounds%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Balazs%22%2C%22lastName%22%3A%22Szappanos%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Maria%20Virginia%22%2C%22lastName%22%3A%22Buchieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrej%22%2C%22lastName%22%3A%22Trauner%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ilaria%22%2C%22lastName%22%3A%22Piazza%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Paola%22%2C%22lastName%22%3A%22Picotti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S%5Cu00e9bastien%22%2C%22lastName%22%3A%22Gagneux%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sonia%22%2C%22lastName%22%3A%22Borrell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brigitte%22%2C%22lastName%22%3A%22Gicquel%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joel%22%2C%22lastName%22%3A%22Lelievre%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Balazs%22%2C%22lastName%22%3A%22Papp%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22The%20mode%20of%20action%20of%20new%20antimicrobial%20compounds%20can%20be%20predicted%20from%20changes%20in%20metabolome%20profiles%20in%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Boosting%20the%20antibiotics%20pipeline%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Antibiotic%20discovery%20requires%20innovative%20phenotypic%20assays%20to%20identify%20the%20mode%20of%20action%20of%20compounds%20during%20large-scale%20drug%20screening.%20Now%2C%20Zampieri%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20et%20al%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20.%20have%20developed%20a%20high-throughput%20method%20to%20systematically%20quantify%20and%20interpret%20dynamic%20metabolome%20responses%20of%20mycobacteria%20to%20new%20antimicrobial%20compounds.%20They%20demonstrate%20how%20one%20can%20infer%20the%20mode%20of%20action%20of%20uncharacterized%20antimycobacterial%20compounds%20by%20comparing%20drug-induced%20metabolic%20responses%20in%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20smegmatis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20.%20Their%20combined%20mass%20spectrometry%5Cu2013based%20metabolomics%20and%20computational%20workflow%20scaled%20with%20the%20size%20of%20typical%20compound%20libraries%20and%20hence%20could%20facilitate%20the%20selection%20of%20antimicrobial%20compound%20leads%20with%20potentially%20new%20modes%20of%20action.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Rapidly%20spreading%20antibiotic%20resistance%20and%20the%20low%20discovery%20rate%20of%20new%20antimicrobial%20compounds%20demand%20more%20effective%20strategies%20for%20early%20drug%20discovery.%20One%20bottleneck%20in%20the%20drug%20discovery%20pipeline%20is%20the%20identification%20of%20the%20modes%20of%20action%20%28MoAs%29%20of%20new%20compounds.%20We%20have%20developed%20a%20rapid%20systematic%20metabolome%20profiling%20strategy%20to%20classify%20the%20MoAs%20of%20bioactive%20compounds.%20The%20method%20predicted%20MoA-specific%20metabolic%20responses%20in%20the%20nonpathogenic%20bacterium%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20smegmatis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20after%20treatment%20with%2062%20reference%20compounds%20with%20known%20MoAs%20and%20different%20metabolic%20and%20nonmetabolic%20targets.%20We%20then%20analyzed%20a%20library%20of%20212%20new%20antimycobacterial%20compounds%20with%20unknown%20MoAs%20from%20a%20drug%20discovery%20effort%20by%20the%20pharmaceutical%20company%20GlaxoSmithKline%20%28GSK%29.%20More%20than%2070%25%20of%20these%20new%20compounds%20induced%20metabolic%20responses%20in%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20M.%20smegmatis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20indicative%20of%20known%20MoAs%2C%20seven%20of%20which%20were%20experimentally%20validated.%20Only%208%25%20%2816%29%20of%20the%20compounds%20appeared%20to%20target%20unconventional%20cellular%20processes%2C%20illustrating%20the%20difficulty%20in%20discovering%20new%20antibiotics%20with%20different%20MoAs%20among%20compounds%20used%20as%20monotherapies.%20For%20six%20of%20the%20GSK%20compounds%20with%20potentially%20new%20MoAs%2C%20the%20metabolome%20profiles%20suggested%20their%20ability%20to%20interfere%20with%20trehalose%20and%20lipid%20metabolism.%20This%20was%20supported%20by%20whole-genome%20sequencing%20of%20spontaneous%20drug-resistant%20mutants%20of%20the%20pathogen%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Mycobacterium%20tuberculosis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20and%20in%20vitro%20compound-proteome%20interaction%20analysis%20for%20one%20of%20these%20compounds.%20Our%20compendium%20of%20drug-metabolome%20profiles%20can%20be%20used%20to%20rapidly%20query%20the%20MoAs%20of%20uncharacterized%20antimicrobial%20compounds%20and%20should%20be%20a%20useful%20resource%20for%20the%20drug%20discovery%20community.%22%2C%22date%22%3A%222018-02-21%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1126%5C%2Fscitranslmed.aal3973%22%2C%22ISSN%22%3A%221946-6234%2C%201946-6242%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscitranslmed.aal3973%22%2C%22collections%22%3A%5B%22DMTSVRD2%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A49%3A51Z%22%7D%7D%2C%7B%22key%22%3A%22ULBCMALW%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%22%2C%22parsedDate%22%3A%222018%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282018%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2452310018300015%27%3EFrom%20the%20metabolic%20profiling%20of%20drug%20response%20to%20drug%20mode%20of%20action%3C%5C%2Fa%3E.%20%3Ci%3ECurrent%20Opinion%20in%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E10%3C%5C%2Fi%3E%2C%2026%5Cu201333.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.coisb.2018.05.005%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22From%20the%20metabolic%20profiling%20of%20drug%20response%20to%20drug%20mode%20of%20action%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2208%5C%2F2018%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.coisb.2018.05.005%22%2C%22ISSN%22%3A%2224523100%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2452310018300015%22%2C%22collections%22%3A%5B%22DMTSVRD2%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A49%3A36Z%22%7D%7D%2C%7B%22key%22%3A%227R9YVX55%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Dubuis%20et%20al.%22%2C%22parsedDate%22%3A%222018-08-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EDubuis%2C%20S.%2C%20Ortmayr%2C%20K.%2C%20%26%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%20%282018%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs42003-018-0111-x%27%3EA%20framework%20for%20large-scale%20metabolome%20drug%20profiling%20links%20coenzyme%20A%20metabolism%20to%20the%20toxicity%20of%20anti-cancer%20drug%20dichloroacetate%3C%5C%2Fa%3E.%20%3Ci%3ECommunications%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E1%3C%5C%2Fi%3E%281%29%2C%20101.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs42003-018-0111-x%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20framework%20for%20large-scale%20metabolome%20drug%20profiling%20links%20coenzyme%20A%20metabolism%20to%20the%20toxicity%20of%20anti-cancer%20drug%20dichloroacetate%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22S%5Cu00e9bastien%22%2C%22lastName%22%3A%22Dubuis%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karin%22%2C%22lastName%22%3A%22Ortmayr%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Metabolic%20profiling%20of%20cell%20line%20collections%20has%20become%20an%20invaluable%20tool%20to%20study%20disease%20etiology%2C%20drug%20modes%20of%20action%20and%20to%20select%20personalized%20treatments.%20However%2C%20large-scale%20in%20vitro%20dynamic%20metabolic%20profiling%20is%20limited%20by%20time-consuming%20sampling%20and%20complex%20measurement%20procedures.%20By%20adapting%20a%20mass%20spectrometry-based%20metabolomics%20workflow%20for%20high-throughput%20profiling%20of%20diverse%20adherent%20mammalian%20cells%2C%20we%20establish%20a%20framework%20for%20the%20rapid%20measurement%20and%20analysis%20of%20drug-induced%20dynamic%20changes%20in%20intracellular%20metabolites.%20This%20methodology%20is%20scalable%20to%20large%20compound%20libraries%20and%20is%20here%20applied%20to%20study%20the%20mechanism%20underlying%20the%20toxic%20effect%20of%20dichloroacetate%20in%20ovarian%20cancer%20cell%20lines.%20System-level%20analysis%20of%20the%20metabolic%20responses%20revealed%20a%20key%20and%20unexpected%20role%20of%20CoA%20biosynthesis%20in%20dichloroacetate%20toxicity%5Cu00a0and%20the%20more%20general%20importance%20of%20CoA%20homeostasis%20across%20diverse%5Cu00a0human%20cell%20lines.%20The%20herein-proposed%20strategy%20for%20high-content%20drug%20metabolic%20profiling%20is%20complementary%20to%20other%20molecular%20profiling%20techniques%2C%20opening%20new%20scientific%20and%20drug-discovery%20opportunities.%22%2C%22date%22%3A%222018-08-03%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1038%5C%2Fs42003-018-0111-x%22%2C%22ISSN%22%3A%222399-3642%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.nature.com%5C%2Farticles%5C%2Fs42003-018-0111-x%22%2C%22collections%22%3A%5B%22DMTSVRD2%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A49%3A17Z%22%7D%7D%5D%7DZampieri, M., Szappanos, B., Buchieri, M. V., Trauner, A., Piazza, I., Picotti, P., Gagneux, S., Borrell, S., Gicquel, B., Lelievre, J., Papp, B., & Sauer, U. (2018). High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds. Science Translational Medicine, 10(429), eaal3973. https://doi.org/10.1126/scitranslmed.aal3973Zampieri, M. (2018). From the metabolic profiling of drug response to drug mode of action. Current Opinion in Systems Biology, 10, 26–33. https://doi.org/10.1016/j.coisb.2018.05.005Dubuis, S., Ortmayr, K., & Zampieri, M. (2018). A framework for large-scale metabolome drug profiling links coenzyme A metabolism to the toxicity of anti-cancer drug dichloroacetate. Communications Biology, 1(1), 101. https://doi.org/10.1038/s42003-018-0111-x
12827833 T65SG2VZ 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22ML8KVAA3%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Fuhrer%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EFuhrer%2C%20T.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20S%5Cu00e9vin%2C%20D.%20C.%2C%20Sauer%2C%20U.%2C%20%26%20Zamboni%2C%20N.%20%282017%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.embopress.org%5C%2Fdoi%5C%2F10.15252%5C%2Fmsb.20167150%27%3EGenomewide%20landscape%20of%20gene%5Cu2013metabolome%20associations%20in%20%3Ci%3EEscherichia%20coli%3C%5C%2Fi%3E%3C%5C%2Fa%3E.%20%3Ci%3EMolecular%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E13%3C%5C%2Fi%3E%281%29%2C%20907.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.15252%5C%2Fmsb.20167150%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Genomewide%20landscape%20of%20gene%5Cu2013metabolome%20associations%20in%20%3Ci%3EEscherichia%20coli%3C%5C%2Fi%3E%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tobias%22%2C%22lastName%22%3A%22Fuhrer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%20C%22%2C%22lastName%22%3A%22S%5Cu00e9vin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicola%22%2C%22lastName%22%3A%22Zamboni%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Metabolism%20is%20one%20of%20the%20best%5Cu2010understood%20cellular%20processes%20whose%20network%20topology%20of%20enzymatic%20reactions%20is%20determined%20by%20an%20organism%27s%20genome.%20The%20influence%20of%20genes%20on%20metabolite%20levels%2C%20however%2C%20remains%20largely%20unknown%2C%20particularly%20for%20the%20many%20genes%20encoding%20non%5Cu2010enzymatic%20proteins.%20Serendipitously%2C%20genomewide%20association%20studies%20explore%20the%20relationship%20between%20genetic%20variants%20and%20metabolite%20levels%2C%20but%20a%20comprehensive%20interaction%20network%20has%20remained%20elusive%20even%20for%20the%20simplest%20single%5Cu2010celled%20organisms.%20Here%2C%20we%20systematically%20mapped%20the%20association%20between%20%3E%5Cu00a03%2C800%20single%5Cu2010gene%20deletions%20in%20the%20bacterium%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Escherichia%20coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20and%20relative%20concentrations%20of%20%3E%5Cu00a07%2C000%20intracellular%20metabolite%20ions.%20Beyond%20expected%20metabolic%20changes%20in%20the%20proximity%20to%20abolished%20enzyme%20activities%2C%20the%20association%20map%20reveals%20a%20largely%20unknown%20landscape%20of%20gene%5Cu2013metabolite%20interactions%20that%20are%20not%20represented%20in%20metabolic%20models.%20Therefore%2C%20the%20map%20provides%20a%20unique%20resource%20for%20assessing%20the%20genetic%20basis%20of%20metabolic%20changes%20and%20conversely%20hypothesizing%20metabolic%20consequences%20of%20genetic%20alterations.%20We%20illustrate%20this%20by%20predicting%20metabolism%5Cu2010related%20functions%20of%2072%20so%20far%20not%20annotated%20genes%20and%20by%20identifying%20key%20genes%20mediating%20the%20cellular%20response%20to%20environmental%20perturbations.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Synopsis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20image%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20metabolome%20of%20%3E%5Cu00a03%2C800%20single%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Escherichia%20coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20gene%20deletion%20mutants%20is%20analyzed.%20The%20obtained%20gene%5Cu2013metabolite%20interaction%20map%20allows%20predicting%20orphan%20gene%20functions%20and%20interpreting%20a%20cell%27s%20response%20to%20environmental%20perturbations.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Systematic%20metabolome%20profiling%20of%20%3E%5Cu00a03%2C800%20single%5Cu2010gene%20deletions%20in%20the%20bacterium%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20E.%5Cu00a0coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20charts%20an%20empirical%20map%20of%20gene%5Cu2013metabolite%20associations.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Metabolic%20changes%20in%20deletion%20mutants%20reveal%20a%20largely%20unknown%20landscape%20of%20gene%5Cu2013metabolite%20interactions%20that%20are%20not%20represented%20in%20metabolic%20models.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Metabolic%20fingerprint%20and%20gene%5Cu2013gene%20similarity%20reveals%20the%20potential%20functionality%20of%2072%20orphan%20genes.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20broad%20applicability%20of%20metabolome%20profiling%20in%20gene%20deletions%20for%20interpreting%20metabolome%20changes%20to%20external%20perturbations%20is%20demonstrated.%22%2C%22date%22%3A%2201%5C%2F2017%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.15252%5C%2Fmsb.20167150%22%2C%22ISSN%22%3A%221744-4292%2C%201744-4292%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.embopress.org%5C%2Fdoi%5C%2F10.15252%5C%2Fmsb.20167150%22%2C%22collections%22%3A%5B%22T65SG2VZ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A52%3A33Z%22%7D%7D%2C%7B%22key%22%3A%22DHRCC8AQ%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Gon%5Cu00e7alves%20et%20al.%22%2C%22parsedDate%22%3A%222017-01-10%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EGon%5Cu00e7alves%2C%20E.%2C%20Raguz%20Nakic%2C%20Z.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Wagih%2C%20O.%2C%20Ochoa%2C%20D.%2C%20Sauer%2C%20U.%2C%20Beltrao%2C%20P.%2C%20%26%20Saez-Rodriguez%2C%20J.%20%282017%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdx.plos.org%5C%2F10.1371%5C%2Fjournal.pcbi.1005297%27%3ESystematic%20Analysis%20of%20Transcriptional%20and%20Post-transcriptional%20Regulation%20of%20Metabolism%20in%20Yeast%3C%5C%2Fa%3E.%20%3Ci%3EPLOS%20Computational%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E13%3C%5C%2Fi%3E%281%29%2C%20e1005297.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1371%5C%2Fjournal.pcbi.1005297%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Systematic%20Analysis%20of%20Transcriptional%20and%20Post-transcriptional%20Regulation%20of%20Metabolism%20in%20Yeast%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Emanuel%22%2C%22lastName%22%3A%22Gon%5Cu00e7alves%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zrinka%22%2C%22lastName%22%3A%22Raguz%20Nakic%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Omar%22%2C%22lastName%22%3A%22Wagih%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22Ochoa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Pedro%22%2C%22lastName%22%3A%22Beltrao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Julio%22%2C%22lastName%22%3A%22Saez-Rodriguez%22%7D%2C%7B%22creatorType%22%3A%22editor%22%2C%22firstName%22%3A%22Kiran%20Raosaheb%22%2C%22lastName%22%3A%22Patil%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222017-1-10%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1371%5C%2Fjournal.pcbi.1005297%22%2C%22ISSN%22%3A%221553-7358%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fdx.plos.org%5C%2F10.1371%5C%2Fjournal.pcbi.1005297%22%2C%22collections%22%3A%5B%22T65SG2VZ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A52%3A13Z%22%7D%7D%2C%7B%22key%22%3A%225YG3MRIH%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Sekar%2C%20K.%2C%20Zamboni%2C%20N.%2C%20%26%20Sauer%2C%20U.%20%282017%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS1367593116301909%27%3EFrontiers%20of%20high-throughput%20metabolomics%3C%5C%2Fa%3E.%20%3Ci%3ECurrent%20Opinion%20in%20Chemical%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E36%3C%5C%2Fi%3E%2C%2015%5Cu201323.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.cbpa.2016.12.006%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Frontiers%20of%20high-throughput%20metabolomics%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Karthik%22%2C%22lastName%22%3A%22Sekar%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicola%22%2C%22lastName%22%3A%22Zamboni%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2202%5C%2F2017%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.cbpa.2016.12.006%22%2C%22ISSN%22%3A%2213675931%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS1367593116301909%22%2C%22collections%22%3A%5B%22T65SG2VZ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A51%3A48Z%22%7D%7D%2C%7B%22key%22%3A%22AY4HRETX%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Enke%2C%20T.%2C%20Chubukov%2C%20V.%2C%20Ricci%2C%20V.%2C%20Piddock%2C%20L.%2C%20%26%20Sauer%2C%20U.%20%282017%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.embopress.org%5C%2Fdoi%5C%2F10.15252%5C%2Fmsb.20167028%27%3EMetabolic%20constraints%20on%20the%20evolution%20of%20antibiotic%20resistance%3C%5C%2Fa%3E.%20%3Ci%3EMolecular%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E13%3C%5C%2Fi%3E%283%29%2C%20917.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.15252%5C%2Fmsb.20167028%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Metabolic%20constraints%20on%20the%20evolution%20of%20antibiotic%20resistance%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tim%22%2C%22lastName%22%3A%22Enke%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Victor%22%2C%22lastName%22%3A%22Chubukov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Vito%22%2C%22lastName%22%3A%22Ricci%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Laura%22%2C%22lastName%22%3A%22Piddock%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Despite%20our%20continuous%20improvement%20in%20understanding%20antibiotic%20resistance%2C%20the%20interplay%20between%20natural%20selection%20of%20resistance%20mutations%20and%20the%20environment%20remains%20unclear.%20To%20investigate%20the%20role%20of%20bacterial%20metabolism%20in%20constraining%20the%20evolution%20of%20antibiotic%20resistance%2C%20we%20evolved%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Escherichia%20coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20growing%20on%20glycolytic%20or%20gluconeogenic%20carbon%20sources%20to%20the%20selective%20pressure%20of%20three%20different%20antibiotics.%20Profiling%20more%20than%20500%20intracellular%20and%20extracellular%20putative%20metabolites%20in%20190%20evolved%20populations%20revealed%20that%20carbon%20and%20energy%20metabolism%20strongly%20constrained%20the%20evolutionary%20trajectories%2C%20both%20in%20terms%20of%20speed%20and%20mode%20of%20resistance%20acquisition.%20To%20interpret%20and%20explore%20the%20space%20of%20metabolome%20changes%2C%20we%20developed%20a%20novel%20constraint%5Cu2010based%20modeling%20approach%20using%20the%20concept%20of%20shadow%20prices.%20This%20analysis%2C%20together%20with%20genome%20resequencing%20of%20resistant%20populations%2C%20identified%20condition%5Cu2010dependent%20compensatory%20mechanisms%20of%20antibiotic%20resistance%2C%20such%20as%20the%20shift%20from%20respiratory%20to%20fermentative%20metabolism%20of%20glucose%20upon%20overexpression%20of%20efflux%20pumps.%20Moreover%2C%20metabolome%5Cu2010based%20predictions%20revealed%20emerging%20weaknesses%20in%20resistant%20strains%2C%20such%20as%20the%20hypersensitivity%20to%20fosfomycin%20of%20ampicillin%5Cu2010resistant%20strains.%20Overall%2C%20resolving%20metabolic%20adaptation%20throughout%20antibiotic%5Cu2010driven%20evolutionary%20trajectories%20opens%20new%20perspectives%20in%20the%20fight%20against%20emerging%20antibiotic%20resistance.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Synopsis%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20image%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Bacterial%20metabolism%20constrains%20the%20evolution%20of%20antibiotic%20resistance.%20A%20modeling%20approach%20is%20developed%20to%20interpret%20the%20functionality%20of%20metabolic%20rewiring%20in%20resistance%5Cu2010evolving%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20E.%5Cu00a0coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20growing%20on%20glycolytic%20or%20gluconeogenic%20carbon%20sources%20from%20metabolomics%20data.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Large%5Cu2010scale%20untargeted%20metabolome%20profiling%20reveals%20metabolic%20adaptations%20in%20190%20evolved%20antibiotic%5Cu2010resistant%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20E.%5Cu00a0coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20populations%2C%20in%20part%20as%20compensation%20for%20consequences%20of%20the%20primary%20resistance%20mechanisms.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Carbon%20and%20energy%20metabolism%20strongly%20constrain%20the%20evolutionary%20trajectories%2C%20both%20in%20terms%20of%20speed%20and%20mode%20of%20resistance%20acquisition.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20A%20novel%20constraint%5Cu2010based%20modeling%20approach%2C%20together%20with%20genome%20re%5Cu2010sequencing%20of%20resistant%20populations%2C%20identifies%20condition%5Cu2010dependent%20compensatory%20mechanisms.%22%2C%22date%22%3A%2203%5C%2F2017%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.15252%5C%2Fmsb.20167028%22%2C%22ISSN%22%3A%221744-4292%2C%201744-4292%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.embopress.org%5C%2Fdoi%5C%2F10.15252%5C%2Fmsb.20167028%22%2C%22collections%22%3A%5B%22T65SG2VZ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A51%3A33Z%22%7D%7D%2C%7B%22key%22%3A%22E2UMDHDL%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Zimmermann%2C%20M.%2C%20Claassen%2C%20M.%2C%20%26%20Sauer%2C%20U.%20%282017%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2211124717304618%27%3ENontargeted%20Metabolomics%20Reveals%20the%20Multilevel%20Response%20to%20Antibiotic%20Perturbations%3C%5C%2Fa%3E.%20%3Ci%3ECell%20Reports%3C%5C%2Fi%3E%2C%20%3Ci%3E19%3C%5C%2Fi%3E%286%29%2C%201214%5Cu20131228.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.celrep.2017.04.002%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Nontargeted%20Metabolomics%20Reveals%20the%20Multilevel%20Response%20to%20Antibiotic%20Perturbations%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Michael%22%2C%22lastName%22%3A%22Zimmermann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Manfred%22%2C%22lastName%22%3A%22Claassen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2205%5C%2F2017%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.celrep.2017.04.002%22%2C%22ISSN%22%3A%2222111247%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2211124717304618%22%2C%22collections%22%3A%5B%22T65SG2VZ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A51%3A06Z%22%7D%7D%2C%7B%22key%22%3A%226KSPVI7K%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20and%20Sauer%22%2C%22parsedDate%22%3A%222017%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20%26%20Sauer%2C%20U.%20%282017%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2452310017301312%27%3EMetabolomics-driven%20understanding%20of%20genotype-phenotype%20relations%20in%20model%20organisms%3C%5C%2Fa%3E.%20%3Ci%3ECurrent%20Opinion%20in%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E6%3C%5C%2Fi%3E%2C%2028%5Cu201336.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.coisb.2017.08.007%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Metabolomics-driven%20understanding%20of%20genotype-phenotype%20relations%20in%20model%20organisms%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2212%5C%2F2017%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.coisb.2017.08.007%22%2C%22ISSN%22%3A%2224523100%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Flinkinghub.elsevier.com%5C%2Fretrieve%5C%2Fpii%5C%2FS2452310017301312%22%2C%22collections%22%3A%5B%22T65SG2VZ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A50%3A13Z%22%7D%7D%5D%7DFuhrer, T., Zampieri, M., Sévin, D. C., Sauer, U., & Zamboni, N. (2017). Genomewide landscape of gene–metabolome associations in Escherichia coli. Molecular Systems Biology, 13(1), 907. https://doi.org/10.15252/msb.20167150Gonçalves, E., Raguz Nakic, Z., Zampieri, M., Wagih, O., Ochoa, D., Sauer, U., Beltrao, P., & Saez-Rodriguez, J. (2017). Systematic Analysis of Transcriptional and Post-transcriptional Regulation of Metabolism in Yeast. PLOS Computational Biology, 13(1), e1005297. https://doi.org/10.1371/journal.pcbi.1005297Zampieri, M., Sekar, K., Zamboni, N., & Sauer, U. (2017). Frontiers of high-throughput metabolomics. Current Opinion in Chemical Biology, 36, 15–23. https://doi.org/10.1016/j.cbpa.2016.12.006Zampieri, M., Enke, T., Chubukov, V., Ricci, V., Piddock, L., & Sauer, U. (2017). Metabolic constraints on the evolution of antibiotic resistance. Molecular Systems Biology, 13(3), 917. https://doi.org/10.15252/msb.20167028Zampieri, M., Zimmermann, M., Claassen, M., & Sauer, U. (2017). Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic Perturbations. Cell Reports, 19(6), 1214–1228. https://doi.org/10.1016/j.celrep.2017.04.002Zampieri, M., & Sauer, U. (2017). Metabolomics-driven understanding of genotype-phenotype relations in model organisms. Current Opinion in Systems Biology, 6, 28–36. https://doi.org/10.1016/j.coisb.2017.08.007
12827833 CFUIGRSU 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22QWNM4MX4%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20and%20Sauer%22%2C%22parsedDate%22%3A%222016-06-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20%26%20Sauer%2C%20U.%20%282016%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fbioinformatics%5C%2Farticle%5C%2F32%5C%2F11%5C%2F1733%5C%2F1743202%27%3EModel-based%20media%20selection%20to%20minimize%20the%20cost%20of%20metabolic%20cooperation%20in%20microbial%20ecosystems%3C%5C%2Fa%3E.%20%3Ci%3EBioinformatics%3C%5C%2Fi%3E%2C%20%3Ci%3E32%3C%5C%2Fi%3E%2811%29%2C%201733%5Cu20131739.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fbioinformatics%5C%2Fbtw062%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Model-based%20media%20selection%20to%20minimize%20the%20cost%20of%20metabolic%20cooperation%20in%20microbial%20ecosystems%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Motivation%3A%20Simple%20forms%20of%20mutualism%20between%20microorganisms%20are%20widespread%20in%20nature.%20Nevertheless%2C%20the%20role%20played%20by%20the%20environmental%20nutrient%20composition%20in%20mediating%20cross-feeding%20in%20microbial%20ecosystems%20is%20still%20poorly%20understood.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Results%3A%20Here%2C%20we%20use%20mixed-integer%20bilevel%20linear%20programming%20to%20investigate%20the%20cost%20of%20sharing%20metabolic%20resources%20in%20microbial%20communities.%20The%20algorithm%20infers%20an%20optimal%20combination%20of%20nutrients%20that%20can%20selectively%20sustain%20synergistic%20growth%20for%20a%20pair%20of%20species%20and%20guarantees%20minimum%20cost%20of%20cross-fed%20metabolites.%20To%20test%20model-based%20predictions%2C%20we%20selected%20a%20pair%20of%20Escherichia%20coli%20single%20gene%20knockouts%20auxotrophic%2C%20respectively%2C%20for%20arginine%20and%20leucine%3A%20%5Cu0394argB%20and%20%5Cu0394leuB%20and%20we%20experimentally%20verified%20that%20model-predicted%20medium%20composition%20significantly%20favors%20mutualism.%20Moreover%2C%20mass%20spectrometry%20profiling%20of%20exchanged%20metabolites%20confirmed%20the%20predicted%20cross-fed%20metabolites%2C%20supporting%20our%20constraint%20based%20modeling%20approach%20as%20a%20promising%20tool%20for%20engineering%20microbial%20consortia.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Availability%20and%20implementation%3A%20The%20software%20is%20freely%20available%20as%20a%20matlab%20script%20in%20the%20Supplementary%20materials.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Contact%3A%20%5Cu00a0zampieri%40imsb.biol.ethz.ch.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Supplementary%20information%3A%20%5Cu00a0Supplementary%20data%20are%20available%20at%20Bioinformatics%20online.%22%2C%22date%22%3A%222016-06-01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Fbioinformatics%5C%2Fbtw062%22%2C%22ISSN%22%3A%221367-4811%2C%201367-4803%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fbioinformatics%5C%2Farticle%5C%2F32%5C%2F11%5C%2F1733%5C%2F1743202%22%2C%22collections%22%3A%5B%22CFUIGRSU%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A53%3A04Z%22%7D%7D%5D%7DZampieri, M., & Sauer, U. (2016). Model-based media selection to minimize the cost of metabolic cooperation in microbial ecosystems. Bioinformatics, 32(11), 1733–1739. https://doi.org/10.1093/bioinformatics/btw062
12827833 T8U88RQ3 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22N8DVUZ89%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Oliveira%20et%20al.%22%2C%22parsedDate%22%3A%222015-04-28%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EOliveira%2C%20A.%20P.%2C%20Ludwig%2C%20C.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Weisser%2C%20H.%2C%20Aebersold%2C%20R.%2C%20%26%20Sauer%2C%20U.%20%282015%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscisignal.2005768%27%3EDynamic%20phosphoproteomics%20reveals%20TORC1-dependent%20regulation%20of%20yeast%20nucleotide%20and%20amino%20acid%20biosynthesis%3C%5C%2Fa%3E.%20%3Ci%3EScience%20Signaling%3C%5C%2Fi%3E%2C%20%3Ci%3E8%3C%5C%2Fi%3E%28374%29.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscisignal.2005768%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Dynamic%20phosphoproteomics%20reveals%20TORC1-dependent%20regulation%20of%20yeast%20nucleotide%20and%20amino%20acid%20biosynthesis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ana%20Paula%22%2C%22lastName%22%3A%22Oliveira%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christina%22%2C%22lastName%22%3A%22Ludwig%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hendrik%22%2C%22lastName%22%3A%22Weisser%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ruedi%22%2C%22lastName%22%3A%22Aebersold%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22The%20effect%20of%20phosphorylation%20on%20metabolic%20enzyme%20activity%20could%20be%20inferred%20by%20correlating%20phosphoproteomics%20and%20metabolomics%20data.%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20How%20phosphorylation%20regulates%20metabolism%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20phosphorylation%20events%20triggered%20directly%20by%20or%20downstream%20of%20the%20protein%20complex%20TORC1%20enable%20yeast%20to%20adjust%20their%20metabolism%20to%20respond%20to%20changes%20in%20nutrient%20availability%20or%20nutritional%20quality.%20Oliveira%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20et%20al.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20subjected%20yeast%20to%20changes%20in%20nutrient%20quality%20or%20to%20treatment%20with%20rapamycin%2C%20an%20inhibitor%20of%20TORC1.%20By%20temporally%20correlating%20changes%20in%20metabolite%20concentrations%20with%20phosphorylation%20events%2C%20they%20identified%20metabolic%20enzymes%20downstream%20of%20TORC1%20and%20inferred%20the%20effect%20of%20phosphorylation%20on%20the%20activity%20of%20these%20enzymes%2C%20which%20included%20enzymes%20involved%20in%20nucleotide%20and%20amino%20acid%20metabolism%20and%20in%20carbohydrate%20storage.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Phosphoproteomics%20studies%20have%20unraveled%20the%20extent%20of%20protein%20phosphorylation%20as%20a%20key%20cellular%20regulation%20mechanism%2C%20but%20assigning%20functionality%20to%20specific%20phosphorylation%20events%20remains%20a%20major%20challenge.%20TORC1%20%28target%20of%20rapamycin%20complex%201%29%20is%20a%20kinase-containing%20protein%20complex%20that%20transduces%20changes%20in%20nutrient%20availability%20into%20phosphorylation%20signaling%20events%20that%20alter%20cell%20growth%20and%20proliferation.%20To%20resolve%20the%20temporal%20sequence%20of%20phosphorylation%20responses%20to%20nutritionally%20and%20chemically%20induced%20changes%20in%20TORC1%20signaling%20and%20to%20identify%20previously%20unknown%20kinase-substrate%20relationships%20in%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Saccharomyces%20cerevisiae%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2C%20we%20performed%20quantitative%20mass%20spectrometry%5Cu2013based%20phosphoproteomic%20analyses%20after%20shifts%20in%20nitrogen%20sources%20and%20rapamycin%20treatment.%20From%20early%20phosphorylation%20events%20that%20were%20consistent%20over%20at%20least%20two%20experimental%20perturbations%2C%20we%20identified%2051%20candidate%20and%2010%20known%20proximal%20targets%20of%20TORC1%20that%20were%20direct%20substrates%20of%20TORC1%20or%20of%20one%20of%20its%20kinase%20or%20phosphatase%20substrates.%20By%20correlating%20these%20phosphoproteomics%20data%20with%20dynamic%20metabolomics%20data%2C%20we%20inferred%20the%20functional%20role%20of%20phosphorylation%20on%20the%20metabolic%20activity%20of%2012%20enzymes%2C%20including%20three%20candidate%20TORC1-proximal%20targets%3A%20Amd1%2C%20which%20is%20involved%20in%20nucleotide%20metabolism%3B%20Hom3%2C%20which%20is%20involved%20in%20amino%20acid%20metabolism%3B%20and%20Tsl1%2C%20which%20mediates%20carbohydrate%20storage.%20Finally%2C%20we%20identified%20the%20TORC1%20substrates%20Sch9%20and%20Atg1%20as%20candidate%20kinases%20that%20phosphorylate%20Amd1%20and%20Hom3%2C%20respectively.%22%2C%22date%22%3A%222015-04-28%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1126%5C%2Fscisignal.2005768%22%2C%22ISSN%22%3A%221945-0877%2C%201937-9145%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscisignal.2005768%22%2C%22collections%22%3A%5B%22T8U88RQ3%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A53%3A33Z%22%7D%7D%5D%7DOliveira, A. P., Ludwig, C., Zampieri, M., Weisser, H., Aebersold, R., & Sauer, U. (2015). Dynamic phosphoproteomics reveals TORC1-dependent regulation of yeast nucleotide and amino acid biosynthesis. Science Signaling, 8(374). https://doi.org/10.1126/scisignal.2005768
12827833 PX6PN8GF 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22ZC265T6I%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Schulz%20et%20al.%22%2C%22parsedDate%22%3A%222014-11-25%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ESchulz%2C%20J.%20C.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Wanka%2C%20S.%2C%20Von%20Mering%2C%20C.%2C%20%26%20Sauer%2C%20U.%20%282014%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscisignal.2005602%27%3ELarge-scale%20functional%20analysis%20of%20the%20roles%20of%20phosphorylation%20in%20yeast%20metabolic%20pathways%3C%5C%2Fa%3E.%20%3Ci%3EScience%20Signaling%3C%5C%2Fi%3E%2C%20%3Ci%3E7%3C%5C%2Fi%3E%28353%29.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscisignal.2005602%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Large-scale%20functional%20analysis%20of%20the%20roles%20of%20phosphorylation%20in%20yeast%20metabolic%20pathways%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Juliane%20Caroline%22%2C%22lastName%22%3A%22Schulz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Stefanie%22%2C%22lastName%22%3A%22Wanka%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Christian%22%2C%22lastName%22%3A%22Von%20Mering%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22An%20integrated%20experimental%20and%20computational%20approach%20identifies%20roles%20for%20protein%20phosphorylation%20in%20yeast%20metabolic%20pathways.%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Mapping%20the%20Metabolome%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20There%20is%20a%20complex%20interplay%20between%20factors%20in%20the%20external%20environment%20of%20a%20cell%20and%20the%20metabolism%20of%20the%20thousands%20of%20molecules%20inside%20a%20cell.%20This%20interplay%20is%20governed%20in%20part%20by%20protein%20phosphorylation.%20Schulz%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20et%20al%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20.%20used%20mass%20spectrometry%20to%20profile%20relative%20concentrations%20of%20hundreds%20of%20metabolites%20in%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Saccharomyces%20cerevisiae%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20yeast%20with%20individual%20deletions%20of%20the%20genes%20encoding%20greater%20that%20100%20kinases%20and%20phosphatases.%20Mapping%20these%20changes%20onto%20a%20network%20of%20metabolic%20pathways%20and%20integrating%20information%20about%20changes%20in%20protein%20phosphorylation%20in%20the%20same%20yeast%20deletion%20strains%20enabled%20predictions%20about%20the%20functional%20relationships%20between%20kinases%20or%20phosphatases%20and%20enzymes%20involved%20in%20cellular%20metabolism.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Protein%20phosphorylation%20is%20a%20widespread%20posttranslational%20modification%20that%20regulates%20almost%20all%20cellular%20functions.%20To%20investigate%20the%20large%20number%20of%20phosphorylation%20events%20with%20unknown%20functions%2C%20we%20monitored%20the%20concentrations%20of%20several%20hundred%20intracellular%20metabolites%20in%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Saccharomyces%20cerevisiae%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20yeast%20strains%20with%20deletions%20of%20118%20kinases%20or%20phosphatases.%20Whereas%20most%20deletion%20strains%20had%20no%20detectable%20difference%20in%20growth%20compared%20to%20wild-type%20yeast%2C%20two-thirds%20of%20deletion%20strains%20had%20alterations%20in%20metabolic%20profiles.%20For%20about%20half%20of%20the%20kinases%20and%20phosphatases%20encoded%20by%20the%20deleted%20genes%2C%20we%20inferred%20specific%20regulatory%20roles%20on%20the%20basis%20of%20knowledge%20about%20the%20affected%20metabolic%20pathways.%20We%20demonstrated%20that%20the%20phosphatase%20Ppq1%20was%20required%20for%20metal%20homeostasis.%20Combining%20metabolomic%20data%20with%20published%20phosphoproteomic%20data%20in%20a%20stoichiometric%20model%20enabled%20us%20to%20predict%20functions%20for%20phosphorylation%20in%20the%20regulation%20of%2047%20enzymes.%20Overall%2C%20we%20provided%20insights%20and%20testable%20predictions%20covering%20greater%20than%20twice%20the%20number%20of%20known%20phosphorylated%20enzymes%20in%20yeast%2C%20suggesting%20extensive%20phosphorylation-dependent%20regulation%20of%20yeast%20metabolism.%22%2C%22date%22%3A%222014-11-25%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1126%5C%2Fscisignal.2005602%22%2C%22ISSN%22%3A%221945-0877%2C%201937-9145%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscisignal.2005602%22%2C%22collections%22%3A%5B%22PX6PN8GF%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A53%3A55Z%22%7D%7D%5D%7DSchulz, J. C., Zampieri, M., Wanka, S., Von Mering, C., & Sauer, U. (2014). Large-scale functional analysis of the roles of phosphorylation in yeast metabolic pathways. Science Signaling, 7(353). https://doi.org/10.1126/scisignal.2005602
12827833 RFM3AGW9 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%227PWX6XIZ%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Schuetz%20et%20al.%22%2C%22parsedDate%22%3A%222012-05-04%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ESchuetz%2C%20R.%2C%20Zamboni%2C%20N.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Heinemann%2C%20M.%2C%20%26%20Sauer%2C%20U.%20%282012%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscience.1216882%27%3EMultidimensional%20Optimality%20of%20Microbial%20Metabolism%3C%5C%2Fa%3E.%20%3Ci%3EScience%3C%5C%2Fi%3E%2C%20%3Ci%3E336%3C%5C%2Fi%3E%286081%29%2C%20601%5Cu2013604.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscience.1216882%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Multidimensional%20Optimality%20of%20Microbial%20Metabolism%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Robert%22%2C%22lastName%22%3A%22Schuetz%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicola%22%2C%22lastName%22%3A%22Zamboni%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthias%22%2C%22lastName%22%3A%22Heinemann%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Uwe%22%2C%22lastName%22%3A%22Sauer%22%7D%5D%2C%22abstractNote%22%3A%22Metabolic%20Networking%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Understanding%20complex%20biological%20networks%2C%20such%20as%20those%20underlying%20cellular%20metabolism%2C%20requires%20evaluation%20not%20only%20of%20the%20network%20connections%20but%20also%20the%20flux%20through%20the%20various%20biochemical%20pathways.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20Schuetz%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20et%20al.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%28p.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20601%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%29%20explored%20the%20evolutionary%20constraints%20that%20appear%20to%20be%20most%20critical%20for%20the%20metabolic%20network%20in%20the%20bacteria%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Escherichia%20coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20using%20a%20combination%20of%20experimental%20tests%20of%20reaction%20flux%20under%20various%20conditions%20along%20with%20mathematical%20modeling.%20As%20a%20pathway%20evolves%2C%20there%20are%20likely%20to%20be%20competing%20objectives%20that%20must%20be%20satisfied.%20Key%20objectives%20for%20the%20bacterium%20were%20strong%20performance%20under%20a%20given%20environmental%20condition%2C%20balanced%20by%20a%20requirement%20for%20adaptability%5Cu2014minimizing%20the%20adjustments%20required%20to%20respond%20to%20changed%20conditions.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20A%20key%20design%20principle%20of%20bacterial%20metabolic%20networks%20is%20optimal%20performance%2C%20but%20not%20at%20the%20expense%20of%20adaptability.%20%5Cn%20%20%20%20%20%20%20%20%20%20%2C%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Although%20the%20network%20topology%20of%20metabolism%20is%20well%20known%2C%20understanding%20the%20principles%20that%20govern%20the%20distribution%20of%20fluxes%20through%20metabolism%20lags%20behind.%20Experimentally%2C%20these%20fluxes%20can%20be%20measured%20by%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%2013%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20C-flux%20analysis%2C%20and%20there%20has%20been%20a%20long-standing%20interest%20in%20understanding%20this%20functional%20network%20operation%20from%20an%20evolutionary%20perspective.%20On%20the%20basis%20of%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%2013%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20C-determined%20fluxes%20from%20nine%20bacteria%20and%20multi-objective%20optimization%20theory%2C%20we%20show%20that%20metabolism%20operates%20close%20to%20the%20Pareto-optimal%20surface%20of%20a%20three-dimensional%20space%20defined%20by%20competing%20objectives.%20Consistent%20with%20flux%20data%20from%20evolved%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Escherichia%20coli%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20%2C%20we%20propose%20that%20flux%20states%20evolve%20under%20the%20trade-off%20between%20two%20principles%3A%20optimality%20under%20one%20given%20condition%20and%20minimal%20adjustment%20between%20conditions.%20These%20principles%20form%20the%20forces%20by%20which%20evolution%20shapes%20metabolic%20fluxes%20in%20microorganisms%5Cu2019%20environmental%20context.%22%2C%22date%22%3A%222012-05-04%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1126%5C%2Fscience.1216882%22%2C%22ISSN%22%3A%220036-8075%2C%201095-9203%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fwww.science.org%5C%2Fdoi%5C%2F10.1126%5C%2Fscience.1216882%22%2C%22collections%22%3A%5B%22RFM3AGW9%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A54%3A59Z%22%7D%7D%2C%7B%22key%22%3A%22MCA7F55M%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Beg%20et%20al.%22%2C%22parsedDate%22%3A%222012%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBeg%2C%20Q.%20K.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Klitgord%2C%20N.%2C%20Collins%2C%20S.%20B.%2C%20Altafini%2C%20C.%2C%20Serres%2C%20M.%20H.%2C%20%26%20Segr%5Cu00e8%2C%20D.%20%282012%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fnar%5C%2Farticle-lookup%5C%2Fdoi%5C%2F10.1093%5C%2Fnar%5C%2Fgks467%27%3EDetection%20of%20transcriptional%20triggers%20in%20the%20dynamics%20of%20microbial%20growth%3A%20application%20to%20the%20respiratorily%20versatile%20bacterium%20Shewanella%20oneidensis%3C%5C%2Fa%3E.%20%3Ci%3ENucleic%20Acids%20Research%3C%5C%2Fi%3E%2C%20%3Ci%3E40%3C%5C%2Fi%3E%2815%29%2C%207132%5Cu20137149.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgks467%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Detection%20of%20transcriptional%20triggers%20in%20the%20dynamics%20of%20microbial%20growth%3A%20application%20to%20the%20respiratorily%20versatile%20bacterium%20Shewanella%20oneidensis%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Qasim%20K.%22%2C%22lastName%22%3A%22Beg%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Niels%22%2C%22lastName%22%3A%22Klitgord%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Sara%20B.%22%2C%22lastName%22%3A%22Collins%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudio%22%2C%22lastName%22%3A%22Altafini%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Margrethe%20H.%22%2C%22lastName%22%3A%22Serres%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%22%2C%22lastName%22%3A%22Segr%5Cu00e8%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%228%5C%2F2012%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Fnar%5C%2Fgks467%22%2C%22ISSN%22%3A%221362-4962%2C%200305-1048%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fnar%5C%2Farticle-lookup%5C%2Fdoi%5C%2F10.1093%5C%2Fnar%5C%2Fgks467%22%2C%22collections%22%3A%5B%22RFM3AGW9%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A54%3A43Z%22%7D%7D%2C%7B%22key%22%3A%22LSZIGZH9%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Facchetti%20et%20al.%22%2C%22parsedDate%22%3A%222012%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EFacchetti%2C%20G.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20%26%20Altafini%2C%20C.%20%282012%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fbmcsystbiol.biomedcentral.com%5C%2Farticles%5C%2F10.1186%5C%2F1752-0509-6-115%27%3EPredicting%20and%20characterizing%20selective%20multiple%20drug%20treatments%20for%20metabolicdiseases%20and%20cancer%3C%5C%2Fa%3E.%20%3Ci%3EBMC%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E6%3C%5C%2Fi%3E%281%29%2C%20115.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2F1752-0509-6-115%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Predicting%20and%20characterizing%20selective%20multiple%20drug%20treatments%20for%20metabolicdiseases%20and%20cancer%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Giuseppe%22%2C%22lastName%22%3A%22Facchetti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudio%22%2C%22lastName%22%3A%22Altafini%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Background%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20In%20the%20field%20of%20drug%20discovery%2C%20assessing%20the%20potential%20of%20multidrug%20therapies%20isa%20difficult%20task%20because%20of%20the%20combinatorial%20complexity%20%28both%20theoretical%20andexperimental%29%20and%20because%20of%20the%20requirements%20on%20the%20selectivity%20of%20the%20therapy.To%20cope%20with%20this%20problem%2C%20we%20have%20developed%20a%20novel%20method%20for%20the%20systematic%20insilico%20investigation%20of%20synergistic%20effects%20of%20currently%20available%20drugs%20ongenome-scale%20metabolic%20networks.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Results%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20algorithm%20finds%20the%20optimal%20combination%20of%20drugs%20which%20guarantees%20theinhibition%20of%20an%20objective%20function%2C%20while%20minimizing%20the%20side%20effect%20on%20the%20othercellular%20processes.%20Two%20different%20applications%20are%20considered%3A%20finding%20drugsynergisms%20for%20human%20metabolic%20diseases%20%28like%20diabetes%2C%20obesity%20and%20hypertension%29and%20finding%20antitumoral%20drug%20combinations%20with%20minimal%20side%20effect%20on%20the%20normalhuman%20cell.%20The%20results%20we%20obtain%20are%20consistent%20with%20some%20of%20the%20availabletherapeutic%20indications%20and%20predict%20new%20multiple%20drug%20treatments.%20A%20clusteranalysis%20on%20all%20possible%20interactions%20among%20the%20currently%20available%20drugsindicates%20a%20limited%20variety%20on%20the%20metabolic%20targets%20for%20the%20approved%20drugs.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Conclusion%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20in%20silico%20prediction%20of%20drug%20synergisms%20can%20represent%20an%20important%20tool%20forthe%20repurposing%20of%20drugs%20in%20a%20realistic%20perspective%20which%20considers%20also%20theselectivity%20of%20the%20therapy.%20Moreover%2C%20for%20a%20more%20profitable%20exploitation%20ofdrug-drug%20interactions%2C%20we%20have%20shown%20that%20also%20experimental%20drugs%20which%20have%20adifferent%20mechanism%20of%20action%20can%20be%20reconsider%20as%20potential%20ingredients%20of%20newmulticompound%20therapeutic%20indications.%20Needless%20to%20say%20the%20clues%20provided%20by%20acomputational%20study%20like%20ours%20need%20in%20any%20case%20to%20be%20thoroughly%20evaluatedexperimentally.%22%2C%22date%22%3A%2212%5C%2F2012%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1186%5C%2F1752-0509-6-115%22%2C%22ISSN%22%3A%221752-0509%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fbmcsystbiol.biomedcentral.com%5C%2Farticles%5C%2F10.1186%5C%2F1752-0509-6-115%22%2C%22collections%22%3A%5B%22RFM3AGW9%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A54%3A25Z%22%7D%7D%5D%7DSchuetz, R., Zamboni, N., Zampieri, M., Heinemann, M., & Sauer, U. (2012). Multidimensional Optimality of Microbial Metabolism. Science, 336(6081), 601–604. https://doi.org/10.1126/science.1216882Beg, Q. K., Zampieri, M., Klitgord, N., Collins, S. B., Altafini, C., Serres, M. H., & Segrè, D. (2012). Detection of transcriptional triggers in the dynamics of microbial growth: application to the respiratorily versatile bacterium Shewanella oneidensis. Nucleic Acids Research, 40(15), 7132–7149. https://doi.org/10.1093/nar/gks467Facchetti, G., Zampieri, M., & Altafini, C. (2012). Predicting and characterizing selective multiple drug treatments for metabolicdiseases and cancer. BMC Systems Biology, 6(1), 115. https://doi.org/10.1186/1752-0509-6-115
12827833 WNGDSNTQ 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%222JM8J5DT%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222011-07-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Altafini%2C%20C.%2C%20Eduati%2C%20F.%2C%20Di%20Camillo%2C%20B.%2C%20Toffolo%2C%20G.%2C%20%26%20De%20Palo%2C%20G.%20%282011%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdigital-library.theiet.org%5C%2Fcontent%5C%2Fjournals%5C%2F10.1049%5C%2Fiet-syb.2009.0050%27%3EAdaptation%20as%20a%20genome-wide%20autoregulatory%20principle%20in%20the%20stress%20response%20of%20yeast%3C%5C%2Fa%3E.%20%3Ci%3EIET%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E5%3C%5C%2Fi%3E%284%29%2C%20269%5Cu2013279.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1049%5C%2Fiet-syb.2009.0050%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Adaptation%20as%20a%20genome-wide%20autoregulatory%20principle%20in%20the%20stress%20response%20of%20yeast%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22M.%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22C.%22%2C%22lastName%22%3A%22Altafini%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22F.%22%2C%22lastName%22%3A%22Eduati%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22B.%22%2C%22lastName%22%3A%22Di%20Camillo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22Toffolo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22G.%22%2C%22lastName%22%3A%22De%20Palo%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222011-07-01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1049%5C%2Fiet-syb.2009.0050%22%2C%22ISSN%22%3A%221751-8849%2C%201751-8857%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fdigital-library.theiet.org%5C%2Fcontent%5C%2Fjournals%5C%2F10.1049%5C%2Fiet-syb.2009.0050%22%2C%22collections%22%3A%5B%22WNGDSNTQ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A55%3A54Z%22%7D%7D%2C%7B%22key%22%3A%22GBKB9LLB%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222011-12-15%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Legname%2C%20G.%2C%20Segr%5Cu00e8%2C%20D.%2C%20%26%20Altafini%2C%20C.%20%282011%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fbioinformatics%5C%2Farticle%5C%2F27%5C%2F24%5C%2F3407%5C%2F306236%27%3EA%20system-level%20approach%20for%20deciphering%20the%20transcriptional%20response%20to%20prion%20infection%3C%5C%2Fa%3E.%20%3Ci%3EBioinformatics%3C%5C%2Fi%3E%2C%20%3Ci%3E27%3C%5C%2Fi%3E%2824%29%2C%203407%5Cu20133414.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fbioinformatics%5C%2Fbtr580%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20system-level%20approach%20for%20deciphering%20the%20transcriptional%20response%20to%20prion%20infection%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Giuseppe%22%2C%22lastName%22%3A%22Legname%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniel%22%2C%22lastName%22%3A%22Segr%5Cu00e8%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudio%22%2C%22lastName%22%3A%22Altafini%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Motivation%3A%20Deciphering%20the%20response%20of%20a%20complex%20biological%20system%20to%20an%20insulting%20event%2C%20at%20the%20gene%20expression%20level%2C%20requires%20adopting%20theoretical%20models%20that%20are%20more%20sophisticated%20than%20a%20one-to-one%20comparison%20%28i.e.%20t-test%29.%20Here%2C%20we%20investigate%20the%20ability%20of%20a%20novel%20reverse%20engineering%20approach%20%28System%20Response%20Inference%29%20to%20unveil%20non-obvious%20transcriptional%20signatures%20of%20the%20system%20response%20induced%20by%20prion%20infection.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Results%3A%20To%20this%20end%2C%20we%20analyze%20previously%20published%20gene%20expression%20data%2C%20from%20which%20we%20extrapolate%20a%20putative%20full-scale%20model%20of%20transcriptional%20gene%5Cu2013gene%20dependencies%20in%20the%20mouse%20central%20nervous%20system.%20Then%2C%20we%20use%20this%20nominal%20model%20to%20interpret%20the%20gene%20expression%20changes%20caused%20by%20prion%20replication%2C%20aiming%20at%20selecting%20the%20genes%20primarily%20influenced%20by%20this%20perturbation.%20Our%20method%20sheds%20light%20on%20the%20mode%20of%20action%20of%20prions%20by%20identifying%20key%20transcripts%20that%20are%20the%20most%20likely%20to%20be%20responsible%20for%20the%20overall%20transcriptional%20rearrangement%20from%20a%20nominal%20regulatory%20network.%20As%20a%20first%20result%20of%20our%20inference%2C%20we%20have%20been%20able%20to%20predict%20known%20targets%20of%20prions%20%28i.e.%20PrPC%29%20and%20to%20unveil%20the%20potential%20role%20of%20previously%20unsuspected%20genes.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Contact%3A%20%5Cu00a0altafini%40sissa.it%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Supplementary%20Information%3A%20%5Cu00a0Supplementary%20data%20are%20available%20at%20Bioinformatics%20online.%22%2C%22date%22%3A%222011-12-15%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Fbioinformatics%5C%2Fbtr580%22%2C%22ISSN%22%3A%221367-4811%2C%201367-4803%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fbioinformatics%5C%2Farticle%5C%2F27%5C%2F24%5C%2F3407%5C%2F306236%22%2C%22collections%22%3A%5B%22WNGDSNTQ%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A55%3A21Z%22%7D%7D%5D%7DZampieri, M., Altafini, C., Eduati, F., Di Camillo, B., Toffolo, G., & De Palo, G. (2011). Adaptation as a genome-wide autoregulatory principle in the stress response of yeast. IET Systems Biology, 5(4), 269–279. https://doi.org/10.1049/iet-syb.2009.0050Zampieri, M., Legname, G., Segrè, D., & Altafini, C. (2011). A system-level approach for deciphering the transcriptional response to prion infection. Bioinformatics, 27(24), 3407–3414. https://doi.org/10.1093/bioinformatics/btr580
12827833 9W6MB6D3 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22N4XCZLS6%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Benetti%20et%20al.%22%2C%22parsedDate%22%3A%222010%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBenetti%2C%20F.%2C%20Gasperini%2C%20L.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20%26%20Legname%2C%20G.%20%282010%29.%20%3Ca%20href%3D%27http%3A%5C%2F%5C%2Fwww.tandfonline.com%5C%2Fdoi%5C%2Ffull%5C%2F10.1517%5C%2F17460440903544449%27%3EGene%20expression%20profiling%20to%20identify%20druggable%20targets%20in%20prion%20diseases%3C%5C%2Fa%3E.%20%3Ci%3EExpert%20Opinion%20on%20Drug%20Discovery%3C%5C%2Fi%3E%2C%20%3Ci%3E5%3C%5C%2Fi%3E%282%29%2C%20177%5Cu2013202.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1517%5C%2F17460440903544449%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Gene%20expression%20profiling%20to%20identify%20druggable%20targets%20in%20prion%20diseases%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Federico%22%2C%22lastName%22%3A%22Benetti%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lisa%22%2C%22lastName%22%3A%22Gasperini%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Giuseppe%22%2C%22lastName%22%3A%22Legname%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%2202%5C%2F2010%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1517%5C%2F17460440903544449%22%2C%22ISSN%22%3A%221746-0441%2C%201746-045X%22%2C%22url%22%3A%22http%3A%5C%2F%5C%2Fwww.tandfonline.com%5C%2Fdoi%5C%2Ffull%5C%2F10.1517%5C%2F17460440903544449%22%2C%22collections%22%3A%5B%229W6MB6D3%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A57%3A29Z%22%7D%7D%5D%7DBenetti, F., Gasperini, L., Zampieri, M., & Legname, G. (2010). Gene expression profiling to identify druggable targets in prion diseases. Expert Opinion on Drug Discovery, 5(2), 177–202. https://doi.org/10.1517/17460440903544449
12827833 6QUMSX9V 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22UUHVL3SV%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222009-07-03%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Legname%2C%20G.%2C%20%26%20Altafini%2C%20C.%20%282009%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdx.plos.org%5C%2F10.1371%5C%2Fjournal.pcbi.1000420%27%3EInvestigating%20the%20Conformational%20Stability%20of%20Prion%20Strains%20through%20a%20Kinetic%20Replication%20Model%3C%5C%2Fa%3E.%20%3Ci%3EPLoS%20Computational%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E5%3C%5C%2Fi%3E%287%29%2C%20e1000420.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1371%5C%2Fjournal.pcbi.1000420%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Investigating%20the%20Conformational%20Stability%20of%20Prion%20Strains%20through%20a%20Kinetic%20Replication%20Model%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Giuseppe%22%2C%22lastName%22%3A%22Legname%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudio%22%2C%22lastName%22%3A%22Altafini%22%7D%2C%7B%22creatorType%22%3A%22editor%22%2C%22firstName%22%3A%22Eugene%20I.%22%2C%22lastName%22%3A%22Shakhnovich%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222009-7-3%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1371%5C%2Fjournal.pcbi.1000420%22%2C%22ISSN%22%3A%221553-7358%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fdx.plos.org%5C%2F10.1371%5C%2Fjournal.pcbi.1000420%22%2C%22collections%22%3A%5B%226QUMSX9V%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A58%3A47Z%22%7D%7D%2C%7B%22key%22%3A%229SYG7JQ4%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Bicciato%20et%20al.%22%2C%22parsedDate%22%3A%222009%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EBicciato%2C%20S.%2C%20Spinelli%2C%20R.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Mangano%2C%20E.%2C%20Ferrari%2C%20F.%2C%20Beltrame%2C%20L.%2C%20Cifola%2C%20I.%2C%20Peano%2C%20C.%2C%20Solari%2C%20A.%2C%20%26%20Battaglia%2C%20C.%20%282009%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fnar%5C%2Farticle-lookup%5C%2Fdoi%5C%2F10.1093%5C%2Fnar%5C%2Fgkp520%27%3EA%20computational%20procedure%20to%20identify%20significant%20overlap%20of%20differentially%20expressed%20and%20genomic%20imbalanced%20regions%20in%20cancer%20datasets%20%5Cu2020%3C%5C%2Fa%3E.%20%3Ci%3ENucleic%20Acids%20Research%3C%5C%2Fi%3E%2C%20%3Ci%3E37%3C%5C%2Fi%3E%2815%29%2C%205057%5Cu20135070.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fnar%5C%2Fgkp520%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22A%20computational%20procedure%20to%20identify%20significant%20overlap%20of%20differentially%20expressed%20and%20genomic%20imbalanced%20regions%20in%20cancer%20datasets%20%5Cu2020%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Silvio%22%2C%22lastName%22%3A%22Bicciato%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Roberta%22%2C%22lastName%22%3A%22Spinelli%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eleonora%22%2C%22lastName%22%3A%22Mangano%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Francesco%22%2C%22lastName%22%3A%22Ferrari%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Luca%22%2C%22lastName%22%3A%22Beltrame%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ingrid%22%2C%22lastName%22%3A%22Cifola%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Clelia%22%2C%22lastName%22%3A%22Peano%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Aldo%22%2C%22lastName%22%3A%22Solari%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Cristina%22%2C%22lastName%22%3A%22Battaglia%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%228%5C%2F2009%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Fnar%5C%2Fgkp520%22%2C%22ISSN%22%3A%221362-4962%2C%200305-1048%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fnar%5C%2Farticle-lookup%5C%2Fdoi%5C%2F10.1093%5C%2Fnar%5C%2Fgkp520%22%2C%22collections%22%3A%5B%226QUMSX9V%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A58%3A29Z%22%7D%7D%2C%7B%22key%22%3A%22WII9DWIZ%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Soranzo%20et%20al.%22%2C%22parsedDate%22%3A%222009%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ESoranzo%2C%20N.%2C%20%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Farina%2C%20L.%2C%20%26%20Altafini%2C%20C.%20%282009%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fbmcsystbiol.biomedcentral.com%5C%2Farticles%5C%2F10.1186%5C%2F1752-0509-3-18%27%3EmRNA%20stability%20and%20the%20unfolding%20of%20gene%20expression%20in%20the%20long-period%20yeast%20metabolic%20cycle%3C%5C%2Fa%3E.%20%3Ci%3EBMC%20Systems%20Biology%3C%5C%2Fi%3E%2C%20%3Ci%3E3%3C%5C%2Fi%3E%281%29%2C%2018.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1186%5C%2F1752-0509-3-18%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22mRNA%20stability%20and%20the%20unfolding%20of%20gene%20expression%20in%20the%20long-period%20yeast%20metabolic%20cycle%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicola%22%2C%22lastName%22%3A%22Soranzo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lorenzo%22%2C%22lastName%22%3A%22Farina%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudio%22%2C%22lastName%22%3A%22Altafini%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Background%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20In%20yeast%2C%20genome-wide%20periodic%20patterns%20associated%20with%20energy-metabolic%20oscillations%20have%20been%20shown%20recently%20for%20both%20short%20%28approx.%2040%20min%29%20and%20long%20%28approx.%20300%20min%29%20periods.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Results%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20dynamical%20regulation%20due%20to%20mRNA%20stability%20is%20found%20to%20be%20an%20important%20aspect%20of%20the%20genome-wide%20coordination%20of%20the%20long-period%20yeast%20metabolic%20cycle.%20It%20is%20shown%20that%20for%20periodic%20genes%2C%20arranged%20in%20classes%20according%20either%20to%20expression%20profile%20or%20to%20function%2C%20the%20pulses%20of%20mRNA%20abundance%20have%20phase%20and%20width%20which%20are%20directly%20proportional%20to%20the%20corresponding%20turnover%20rates.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20Conclusion%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20%20%20The%20cascade%20of%20events%20occurring%20during%20the%20yeast%20metabolic%20cycle%20%28and%20their%20correlation%20with%20mRNA%20turnover%29%20reflects%20to%20a%20large%20extent%20the%20gene%20expression%20program%20observable%20in%20other%20dynamical%20contexts%20such%20as%20the%20response%20to%20stresses%5C%2Fstimuli.%22%2C%22date%22%3A%2212%5C%2F2009%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1186%5C%2F1752-0509-3-18%22%2C%22ISSN%22%3A%221752-0509%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fbmcsystbiol.biomedcentral.com%5C%2Farticles%5C%2F10.1186%5C%2F1752-0509-3-18%22%2C%22collections%22%3A%5B%226QUMSX9V%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A58%3A01Z%22%7D%7D%5D%7DZampieri, M., Legname, G., & Altafini, C. (2009). Investigating the Conformational Stability of Prion Strains through a Kinetic Replication Model. PLoS Computational Biology, 5(7), e1000420. https://doi.org/10.1371/journal.pcbi.1000420Bicciato, S., Spinelli, R., Zampieri, M., Mangano, E., Ferrari, F., Beltrame, L., Cifola, I., Peano, C., Solari, A., & Battaglia, C. (2009). A computational procedure to identify significant overlap of differentially expressed and genomic imbalanced regions in cancer datasets †. Nucleic Acids Research, 37(15), 5057–5070. https://doi.org/10.1093/nar/gkp520Soranzo, N., Zampieri, M., Farina, L., & Altafini, C. (2009). mRNA stability and the unfolding of gene expression in the long-period yeast metabolic cycle. BMC Systems Biology, 3(1), 18. https://doi.org/10.1186/1752-0509-3-18
12827833 I4VDPBMM 1 apa 50 default title Zampieri, M. 117 https://www.zampierilab.org/wp-content/plugins/zotpress/ %7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%22PHPPE7W4%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222008-07-01%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Soranzo%2C%20N.%2C%20%26%20Altafini%2C%20C.%20%282008%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fbioinformatics%5C%2Farticle%5C%2F24%5C%2F13%5C%2F1510%5C%2F237960%27%3EDiscerning%20static%20and%20causal%20interactions%20in%20genome-wide%20reverse%20engineering%20problems%3C%5C%2Fa%3E.%20%3Ci%3EBioinformatics%3C%5C%2Fi%3E%2C%20%3Ci%3E24%3C%5C%2Fi%3E%2813%29%2C%201510%5Cu20131515.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1093%5C%2Fbioinformatics%5C%2Fbtn220%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Discerning%20static%20and%20causal%20interactions%20in%20genome-wide%20reverse%20engineering%20problems%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicola%22%2C%22lastName%22%3A%22Soranzo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudio%22%2C%22lastName%22%3A%22Altafini%22%7D%5D%2C%22abstractNote%22%3A%22Abstract%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Background%3A%20In%20the%20past%20years%20devising%20methods%20for%20discovering%20gene%20regulatory%20mechanisms%20at%20a%20genome-wide%20level%20has%20become%20a%20fundamental%20topic%20in%20the%20field%20of%20systems%20biology.%20The%20aim%20is%20to%20infer%20gene-gene%20interactions%20in%20an%20increasingly%20sophisticated%20and%20reliable%20way%20through%20the%20continuous%20improvement%20of%20reverse%20engineering%20algorithms%20exploiting%20microarray%20data.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Motivation%3A%20This%20work%20is%20inspired%20by%20the%20several%20studies%20suggesting%20that%20coexpression%20is%20mostly%20related%20to%20%5Cu2018static%5Cu2019%20stable%20binding%20relationships%2C%20like%20belonging%20to%20the%20same%20protein%20complex%2C%20rather%20than%20other%20types%20of%20interactions%20more%20of%20a%20%5Cu2018causal%5Cu2019%20and%20transient%20nature%20%28e.g.%20transcription%20factor%5Cu2013binding%20site%20interactions%29.%20The%20aim%20of%20this%20work%20is%20to%20verify%20if%20direct%20or%20conditional%20network%20inference%20algorithms%20%28e.g.%20Pearson%20correlation%20for%20the%20former%2C%20partial%20Pearson%20correlation%20for%20the%20latter%29%20are%20indeed%20useful%20in%20discerning%20static%20from%20causal%20dependencies%20in%20artificial%20and%20real%20gene%20networks%20%28derived%20from%20Escherichia%20coli%20and%20Saccharomyces%20cerevisiae%29.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Results%3A%20Even%20in%20the%20regime%20of%20weak%20inference%20power%20we%20have%20to%20work%20in%2C%20our%20analysis%20confirms%20the%20differences%20in%20the%20performances%20of%20the%20algorithms%3A%20direct%20methods%20are%20more%20robust%20in%20detecting%20stable%20interactions%2C%20conditional%20ones%20are%20better%20for%20causal%20interactions%20especially%20in%20presence%20of%20combinatorial%20transcriptional%20regulation.%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Contact%3A%20%5Cu00a0altafini%40sissa.it%20%5Cn%20%20%20%20%20%20%20%20%20%20%20%20Supplementary%20information%3A%20%5Cu00a0Supplementary%20data%20are%20available%20at%20Bioinformatics%20online.%22%2C%22date%22%3A%222008-07-01%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1093%5C%2Fbioinformatics%5C%2Fbtn220%22%2C%22ISSN%22%3A%221367-4811%2C%201367-4803%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Facademic.oup.com%5C%2Fbioinformatics%5C%2Farticle%5C%2F24%5C%2F13%5C%2F1510%5C%2F237960%22%2C%22collections%22%3A%5B%22I4VDPBMM%22%5D%2C%22dateModified%22%3A%222023-10-26T09%3A00%3A02Z%22%7D%7D%2C%7B%22key%22%3A%229IXREYUH%22%2C%22library%22%3A%7B%22id%22%3A12827833%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Zampieri%20et%20al.%22%2C%22parsedDate%22%3A%222008-08-20%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%202%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EZampieri%2C%20M.%3C%5C%2Fstrong%3E%2C%20Soranzo%2C%20N.%2C%20Bianchini%2C%20D.%2C%20%26%20Altafini%2C%20C.%20%282008%29.%20%3Ca%20href%3D%27https%3A%5C%2F%5C%2Fdx.plos.org%5C%2F10.1371%5C%2Fjournal.pone.0002981%27%3EOrigin%20of%20Co-Expression%20Patterns%20in%20E.coli%20and%20S.cerevisiae%20Emerging%20from%20Reverse%20Engineering%20Algorithms%3C%5C%2Fa%3E.%20%3Ci%3EPLoS%20ONE%3C%5C%2Fi%3E%2C%20%3Ci%3E3%3C%5C%2Fi%3E%288%29%2C%20e2981.%20https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1371%5C%2Fjournal.pone.0002981%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Origin%20of%20Co-Expression%20Patterns%20in%20E.coli%20and%20S.cerevisiae%20Emerging%20from%20Reverse%20Engineering%20Algorithms%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mattia%22%2C%22lastName%22%3A%22Zampieri%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Nicola%22%2C%22lastName%22%3A%22Soranzo%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daniele%22%2C%22lastName%22%3A%22Bianchini%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Claudio%22%2C%22lastName%22%3A%22Altafini%22%7D%2C%7B%22creatorType%22%3A%22editor%22%2C%22firstName%22%3A%22Mark%22%2C%22lastName%22%3A%22Isalan%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222008-8-20%22%2C%22language%22%3A%22en%22%2C%22DOI%22%3A%2210.1371%5C%2Fjournal.pone.0002981%22%2C%22ISSN%22%3A%221932-6203%22%2C%22url%22%3A%22https%3A%5C%2F%5C%2Fdx.plos.org%5C%2F10.1371%5C%2Fjournal.pone.0002981%22%2C%22collections%22%3A%5B%22I4VDPBMM%22%5D%2C%22dateModified%22%3A%222023-10-26T08%3A59%3A38Z%22%7D%7D%5D%7DZampieri, M., Soranzo, N., & Altafini, C. (2008). Discerning static and causal interactions in genome-wide reverse engineering problems. Bioinformatics, 24(13), 1510–1515. https://doi.org/10.1093/bioinformatics/btn220Zampieri, M., Soranzo, N., Bianchini, D., & Altafini, C. (2008). Origin of Co-Expression Patterns in E.coli and S.cerevisiae Emerging from Reverse Engineering Algorithms. PLoS ONE, 3(8), e2981. https://doi.org/10.1371/journal.pone.0002981