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DOI: 10.4230/LIPIcs.WABI.2018.18

Differentially Mutated Subnetworks Discovery

Authors: Morteza Chalabi Hajkarim, Eli Upfal, and Fabio Vandin

Published in: LIPIcs, Volume 113, 18th International Workshop on Algorithms in Bioinformatics (WABI 2018)

Abstract

We study the problem of identifying differentially mutated subnetworks of a large gene-gene interaction network, that is, subnetworks that display a significant difference in mutation frequency in two sets of cancer samples. We formally define the associated computational problem and show that the problem is NP-hard. We propose a novel and efficient algorithm, called DAMOKLE to identify differentially mutated subnetworks given genome-wide mutation data for two sets of cancer samples. We prove that DAMOKLE identifies subnetworks with a statistically significant difference in mutation frequency when the data comes from a reasonable generative model, provided enough samples are available. We test DAMOKLE on simulated and real data, showing that DAMOKLE does indeed find subnetworks with significant differences in mutation frequency and that it provides novel insights not obtained by standard methods.

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Morteza Chalabi Hajkarim, Eli Upfal, and Fabio Vandin. Differentially Mutated Subnetworks Discovery. In 18th International Workshop on Algorithms in Bioinformatics (WABI 2018). Leibniz International Proceedings in Informatics (LIPIcs), Volume 113, pp. 18:1-18:14, Schloss Dagstuhl – Leibniz-Zentrum für Informatik (2018)

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@InProceedings{hajkarim_et_al:LIPIcs.WABI.2018.18,
  author =	{Hajkarim, Morteza Chalabi and Upfal, Eli and Vandin, Fabio},
  title =	{{Differentially Mutated Subnetworks Discovery}},
  booktitle =	{18th International Workshop on Algorithms in Bioinformatics (WABI 2018)},
  pages =	{18:1--18:14},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-082-8},
  ISSN =	{1868-8969},
  year =	{2018},
  volume =	{113},
  editor =	{Parida, Laxmi and Ukkonen, Esko},
  publisher =	{Schloss Dagstuhl -- Leibniz-Zentrum f{\"u}r Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{https://drops.dagstuhl.de/entities/document/10.4230/LIPIcs.WABI.2018.18},
  URN =		{urn:nbn:de:0030-drops-93202},
  doi =		{10.4230/LIPIcs.WABI.2018.18},
  annote =	{Keywords: Cancer genomics, network analysis, combinatorial algorithm}
}

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Differentially Mutated Subnetworks Discovery

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