PhosphoDisco: A Toolkit for Co-regulated Phosphorylation Module Discovery in Phosphoproteomic Data.
PhosphoDisco: A Toolkit for Co-regulated Phosphorylation Module Discovery in Phosphoproteomic Data.
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DOI：
10.1016/j.mcpro.2023.100596
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发表时间：
2023-08
影响因子：
7
通讯作者：
Ruggles, Kelly, V
中科院分区：
文献类型：
--
作者：
Schraink, Tobias;Blumenberg, Lili;Hussey, Grant;George, Sabrina;Miller, Brecca;Mathew, Nithu;Gonzalez-Robles, Tania J.;Sviderskiy, Vladislav;Papagiannakopoulos, Thales;Possemato, Richard;Fenyo, David;Ruggles, Kelly, V
Kinases are key players in cancer-relevant pathways and are the targets of many successful precision cancer therapies. Phosphoproteomics is a powerful approach to study kinase activity and has been used increasingly for the characterization of tumor samples leading to the identification of novel chemotherapeutic targets and biomarkers. Finding co-regulated phosphorylation sites which represent potential kinase-substrate sets or members of the same signaling pathway allows us to harness these data to identify clinically relevant and targetable alterations in signaling cascades. Unfortunately, studies have found that databases of co-regulated phosphorylation sites are only experimentally supported in a small number of substrate sets. To address the inherent challenge of defining co-regulated phosphorylation modules relevant to a given dataset, we developed PhosphoDisco, a toolkit for determining co-regulated phosphorylation modules. We applied this approach to tandem mass spectrometry based phosphoproteomic data for breast and non-small cell lung cancer and identified canonical as well as putative new phosphorylation site modules. Our analysis identified several interesting modules in each cohort. Among these was a new cell cycle checkpoint module enriched in basal breast cancer samples and a module of PRKC isozymes putatively co-regulated by CDK12 in lung cancer. We demonstrate that modules defined by PhosphoDisco can be used to further personalized cancer treatment strategies by establishing active signaling pathways in a given patient tumor or set of tumors, and in providing new ways to classify tumors based on signaling activity. PhosphoDisco is a computational approach to define co-regulated phosphosites. Implementation finds signaling modules in breast and non-small cell lung cancer. Identified a cell cycle checkpoint module in enriched basal breast tumors. PRKC-associated and proliferative enriched modules found in lung tumors. Schraink, Blumenberg, and Hussey et al., demonstrate the use of PhosphoDisco, a newly developed tookit for the identification of co-regulated phosphorylation sites from tandem mass spectrometry–based phosphoproteomic data. Using data from breast and non-small cell lung cancers they identify several clinically relevant phosphorylation modules including a cell cycle checkpoint module enriched in basal breast cancer samples and a module of PRKC isozymes putatively co-regulated by CDK12 in lung cancer.
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影响因子：
16.6
作者：
Huang KL;Li S;Mertins P;Cao S;Gunawardena HP;Ruggles KV;Mani DR;Clauser KR;Tanioka M;Usary J;Kavuri SM;Xie L;Yoon C;Qiao JW;Wrobel J;Wyczalkowski MA;Erdmann-Gilmore P;Snider JE;Hoog J;Singh P;Niu B;Guo Z;Sun SQ;Sanati S;Kawaler E;Wang X;Scott A;Ye K;McLellan MD;Wendl MC;Malovannaya A;Held JM;Gillette MA;Fenyö D;Kinsinger CR;Mesri M;Rodriguez H;Davies SR;Perou CM;Ma C;Reid Townsend R;Chen X;Carr SA;Ellis MJ;Ding L
通讯作者：
Ding L
影响因子：
7
作者：
Arshad, Osama A.;Danna, Vincent;McDermott, Jason E.
通讯作者：
McDermott, Jason E.
影响因子：
8
作者：
Dean, J. L.;Thangavel, C.;Knudsen, E. S.
通讯作者：
Knudsen, E. S.
影响因子：
8
作者：
Kennedy, Sean P.;O'Neill, Michael;Hennessy, Bryan T.
通讯作者：
Hennessy, Bryan T.
影响因子：
64.5
作者：
Gillette, Michael A.;Satpathy, Shankha;Carr, Steven A.
通讯作者：
Carr, Steven A.