@article{7554adc5638b456f8534c2771cc445e3,
title = "Causal interactions from proteomic profiles: Molecular data meet pathway knowledge",
abstract = "We present a computational method to infer causal mechanisms in cell biology by analyzing changes in high-throughput proteomic profiles on the background of prior knowledge captured in biochemical reaction knowledge bases. The method mimics a biologist's traditional approach of explaining changes in data using prior knowledge but does this at the scale of hundreds of thousands of reactions. This is a specific example of how to automate scientific reasoning processes and illustrates the power of mapping from experimental data to prior knowledge via logic programming. The identified mechanisms can explain how experimental and physiological perturbations, propagating in a network of reactions, affect cellular responses and their phenotypic consequences. Causal pathway analysis is a powerful and flexible discovery tool for a wide range of cellular profiling data types and biological questions. The automated causation inference tool, as well as the source code, are freely available at http://causalpath.org.",
keywords = "DSML 3: Development/Pre-production: Data science output has been rolled out/validated across multiple domains/problems, cancer, causal pathway analysis, proteomics",
author = "{\"O}zg{\"u}n Babur and Augustin Luna and Anil Korkut and Funda Durupinar and Siper, {Metin Can} and Ugur Dogrusoz and {Vaca Jacome}, {Alvaro Sebastian} and Ryan Peckner and Christianson, {Karen E.} and Jaffe, {Jacob D.} and Spellman, {Paul T.} and Aslan, {Joseph E.} and Chris Sander and Emek Demir",
note = "Funding Information: We thank Hannah Manning and Olga Nikolova for critical reading of the manuscript. This work was sponsored by DARPA under the Big Mechanism Program (contract W911NF-14-C-0119 ) and the U.S. Army Research Office (contract ACC-APG_RTP W911NF) , and by NIH grants R01HL146549 (to J.E.A.), U41HG006623 (Pathway Commons), and P41GM103504 (National Resource for Network Biology). A.K. is supported by MD Anderson Cancer Center support grant P30 CA016672 (Bioinformatics Shared Resource) and by an OCRA collaborative research grant. U.D. is supported by the Scientific and Technological Research Council of Turkey (grant 118E131 ). The results published here are in part based upon data generated by the Clinical Proteomic Tumor Analysis Consortium (NCI/NIH) and TCGA Research Network: http://cancergenome.nih.gov/ . Funding Information: We thank Hannah Manning and Olga Nikolova for critical reading of the manuscript. This work was sponsored by DARPA under the Big Mechanism Program (contract W911NF-14-C-0119) and the U.S. Army Research Office (contract ACC-APG_RTP W911NF), and by NIH grants R01HL146549 (to J.E.A.), U41HG006623 (Pathway Commons), and P41GM103504 (National Resource for Network Biology). A.K. is supported by MD Anderson Cancer Center support grant P30 CA016672 (Bioinformatics Shared Resource) and by an OCRA collaborative research grant. U.D. is supported by the Scientific and Technological Research Council of Turkey (grant 118E131). The results published here are in part based upon data generated by the Clinical Proteomic Tumor Analysis Consortium (NCI/NIH) and TCGA Research Network: http://cancergenome.nih.gov/. ?.B. and A.K. conceived the idea. ?.B. designed and developed the method and performed all the analyses with help from A.K. A.L. J.E.A. and U.D. F.D. designed and developed the web service with help from M.C.S. and U.D. A.S.V.J. R.P. and K.E.C. contributed to the analysis of the PC3 drug perturbation dataset under the supervision of J.D.J. P.T.S. supervised the validation study on breast cancer cell lines. E.D. and C.S. supervised the project. ?.B. E.D. A.L. C.S. and J.E.A. wrote the manuscript with help from F.D. U.D. and A.K. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = jun,
day = "11",
doi = "10.1016/j.patter.2021.100257",
language = "English (US)",
volume = "2",
journal = "Patterns",
issn = "2666-3899",
publisher = "Cell Press",
number = "6",
}