Location via proxy:   [ UP ]  
[Report a bug]   [Manage cookies]                
skip to main content
10.1145/2808719.2808728acmconferencesArticle/Chapter ViewAbstractPublication PagesbcbConference Proceedingsconference-collections
research-article

Estimating reachability in dense biological networks

Published:09 September 2015Publication History

ABSTRACT

Biological networks provide a holistic view for modeling and analysis of interactions among various kinds of gene products. Finding whether a signal can successfully arrive at a target gene from a given source gene is one of the key problems on biological networks. This is also known as the reachability problem. Computing the probability of signal reachability is a #P-complete problem. This complexity stems from the inherent uncertainty of the interactions. Existing methods fail to scale to large and dense networks. In this paper, we develop a novel method to estimate the reachability probability in probabilistic biological networks. We develop a general theory for utilizing Monte Carlo sampling to solve this problem with a mathematically proven confidence bound on the result. We present three alternative sampling approaches which follow our theory. We experimentally validate our theory, and compare the performance of our method with the state of the art PReach method. We finally use our method to analyze reachability in cell growth and death pathways in different cancer types, which was impossible using existing methods due to the large scale of the networks.

References

  1. Joel S Bader, Amitabha Chaudhuri, Jonathan M Rothberg, and John Chant. Gaining confidence in high-throughput protein interaction networks. Nature biotechnology, 22(1):78--85, 2001.Google ScholarGoogle ScholarCross RefCross Ref
  2. Roded Sharan, Silpa Suthram, Ryan M Kelley, Tanja Kuhn, Scott McCuine, Peter Uetz, Taylor Sittler, Richard M Karp, and Trey Ideker. Conserved patterns of protein interaction in multiple species. Proceedings of the National Academy of Sciences of the United States of America, 102(6):1974--1979, 2005.Google ScholarGoogle ScholarCross RefCross Ref
  3. Oved Ourfali, Tomer Shlomi, Trey Ideker, Eytan Ruppin, and Roded Sharan. Spine: a framework for signaling-regulatory pathway inference from cause-effect experiments. Bioinformatics, 23(13):i359--i366, 2007. Google ScholarGoogle ScholarDigital LibraryDigital Library
  4. Chad L Myers, Drew Robson, Adam Wible, Matthew A Hibbs, Camelia Chiriac, Chandra L Theesfeld, Kara Dolinski, and Olga G Troyanskaya. Discovery of biological networks from diverse functional genomic data. Genome biology, 6(13):R114, 2005.Google ScholarGoogle ScholarCross RefCross Ref
  5. Nir Friedman. Inferring cellular networks using probabilistic graphical models. Science, 303(5659):799--805, 2004.Google ScholarGoogle ScholarCross RefCross Ref
  6. Irit Gat-Viks, Amos Tanay, Daniela Raijman, and Ron Shamir. A probabilistic methodology for integrating knowledge and experiments on biological networks. Journal of Computational Biology, 13(2):165--181, 2006.Google ScholarGoogle ScholarCross RefCross Ref
  7. Jacob Scott, Trey Ideker, Richard M Karp, and Roded Sharan. Efficient algorithms for detecting signaling pathways in protein interaction networks. Journal of Computational Biology, 13(2):133--144, 2006.Google ScholarGoogle ScholarCross RefCross Ref
  8. Andreas Zanzoni, Luisa Montecchi-Palazzi, Michele Quondam, Gabriele Ausiello, Manuela Helmer-Citterich, and Gianni Cesareni. Mint: a molecular interaction database. FEBS letters, 513(1):135--140, 2002.Google ScholarGoogle ScholarCross RefCross Ref
  9. Damian Szklarczyk, Andrea Franceschini, Michael Kuhn, Milan Simonovic, Alexander Roth, Pablo Minguez, Tobias Doerks, Manuel Stark, Jean Muller, Peer Bork, et al. The string database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic acids research, 39(suppl 1):D561--D568, 2011.Google ScholarGoogle Scholar
  10. Andrei Todor, Haitham Gabr, Alin Dobra, and Tamer Kahveci. Large scale analysis of signal reachability. Bioinformatics, 30(12):i96--i104, 2014.Google ScholarGoogle ScholarCross RefCross Ref
  11. J Scott Provan and Michael O Ball. The complexity of counting cuts and of computing the probability that a graph is connected. SIAM Journal on Computing, 12(4):777--788, 1983.Google ScholarGoogle ScholarCross RefCross Ref
  12. Jason I Brown and Charles J Colbourn. Non-stanley bounds for network reliability. Journal of Algebraic Combinatorics, 5(1):13--36, 1996. Google ScholarGoogle ScholarDigital LibraryDigital Library
  13. Thore Husfeldt and Nina Taslaman. The exponential time complexity of computing the probability that a graph is connected. In Parameterized and Exact Computation, pages 192--203. Springer, 2010.Google ScholarGoogle ScholarCross RefCross Ref
  14. Haitham Gabr, Andrei Todor, Helia Zandi, Alin Dobra, and Tamer Kahveci. Preach: reachability in probabilistic signaling networks. In Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics, page 3. ACM, 2013. Google ScholarGoogle ScholarDigital LibraryDigital Library
  15. Malcolm C Easton and CK Wong. Sequential destruction method for monte carlo evaluation of system reliability. Reliability, IEEE Transactions on, 29(1):27--32, 1980.Google ScholarGoogle Scholar
  16. George S Fishman. A monte carlo sampling plan for estimating network reliability. Operations Research, 34(4):581--594, 1986. Google ScholarGoogle ScholarDigital LibraryDigital Library
  17. Richard M. Karp and Michael G. Luby. A new monte-carlo method for estimating the failure probability of an. Technical report, University of California at Berkeley, Berkeley, CA, USA, 1983. Google ScholarGoogle ScholarDigital LibraryDigital Library
  18. Hiromitsu Kumamoto, Kazuo Tanaka, and Koichi Inoue. Efficient evaluation of system reliability by monte carlo method. Reliability, IEEE Transactions on, 26(5):311--315, 1977.Google ScholarGoogle Scholar
  19. Ke Zhu, Wenjie Zhang, Gaoping Zhu, Ying Zhang, and Xuemin Lin. Bmc: an efficient method to evaluate probabilistic reachability queries. In Database Systems for Advanced Applications, pages 434--449. Springer, 2011. Google ScholarGoogle ScholarDigital LibraryDigital Library
  20. Thomas D Pfister, William C Reinhold, Keli Agama, Shalu Gupta, Sonny A Khin, Robert J Kinders, Ralph E Parchment, Joseph E Tomaszewski, James H Doroshow, and Yves Pommier. Topoisomerase i levels in the nci-60 cancer cell line panel determined by validated elisa and microarray analysis and correlation with indenoisoquinoline sensitivity. Molecular cancer therapeutics, 8(7):1878--1884, 2009.Google ScholarGoogle Scholar
  21. David G Rees. Essential statistics, volume 50. CRC Press, 2000.Google ScholarGoogle Scholar
  22. Tomer Shlomi, Daniel Segal, Eytan Ruppin, and Roded Sharan. Qpath: a method for querying pathways in a protein-protein interaction network. BMC bioinformatics, 7(1):199, 2006.Google ScholarGoogle ScholarCross RefCross Ref
  23. Albert-László Barabási and Réka Albert. Emergence of scaling in random networks. science, 286(5439):509--512, 1999.Google ScholarGoogle Scholar
  24. Hawoong Jeong, Bálint Tombor, Réka Albert, Zoltan N Oltvai, and A-L Barabási. The large-scale organization of metabolic networks. Nature, 407(6804):651--654, 2000.Google ScholarGoogle ScholarCross RefCross Ref
  25. Soon-Hyung Yook, Zoltán N Oltvai, and Albert-László Barabási. Functional and topological characterization of protein interaction networks. Proteomics, 4(4):928--942, 2004.Google ScholarGoogle ScholarCross RefCross Ref
  26. Andrei Todor, Alin Dobra, and Tamer Kahveci. Uncertain interactions affect degree distribution of biological networks. In Bioinformatics and Biomedicine (BIBM), 2012 IEEE International Conference on, pages 1--5. IEEE, 2012. Google ScholarGoogle ScholarDigital LibraryDigital Library
  27. Jonathan M Lee and Alan Bernstein. Apoptosis, cancer and the p53 tumour suppressor gene. Cancer and Metastasis Reviews, 14(2):149--161, 1995.Google ScholarGoogle ScholarCross RefCross Ref
  28. Richard J Bold, Paula M Termuhlen, and David J McConkey. Apoptosis, cancer and cancer therapy. Surgical oncology, 6(3):133--142, 1997.Google ScholarGoogle ScholarCross RefCross Ref
  29. John FR Kerr, Clay M Winterford, and Brian V Harmon. Apoptosis. its significance in cancer and cancer therapy. Cancer, 73(8):2013--2026, 1994.Google ScholarGoogle ScholarCross RefCross Ref
  30. Dooniya Shaikh, Qiyuan Zhou, Tianji Chen, Joyce Christina F Ibe, J Usha Raj, and Guofei Zhou. camp-dependent protein kinase is essential for hypoxia-mediated epithelial--mesenchymal transition, migration, and invasion in lung cancer cells. Cellular signalling, 24(12):2396--2406, 2012.Google ScholarGoogle ScholarCross RefCross Ref
  31. Hellinida Thomadaki and Andreas Scorilas. Bcl2 family of apoptosis-related genes: functions and clinical implications in cancer. Critical reviews in clinical laboratory sciences, 43(1):1--67, 2006.Google ScholarGoogle Scholar

Index Terms

  1. Estimating reachability in dense biological networks

          Recommendations

          Comments

          Login options

          Check if you have access through your login credentials or your institution to get full access on this article.

          Sign in
          • Published in

            cover image ACM Conferences
            BCB '15: Proceedings of the 6th ACM Conference on Bioinformatics, Computational Biology and Health Informatics
            September 2015
            683 pages
            ISBN:9781450338530
            DOI:10.1145/2808719

            Copyright © 2015 ACM

            Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. Copyrights for components of this work owned by others than ACM must be honored. Abstracting with credit is permitted. To copy otherwise, or republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. Request permissions from [email protected]

            Publisher

            Association for Computing Machinery

            New York, NY, United States

            Publication History

            • Published: 9 September 2015

            Permissions

            Request permissions about this article.

            Request Permissions

            Check for updates

            Qualifiers

            • research-article

            Acceptance Rates

            BCB '15 Paper Acceptance Rate48of141submissions,34%Overall Acceptance Rate254of885submissions,29%

          PDF Format

          View or Download as a PDF file.

          PDF

          eReader

          View online with eReader.

          eReader