Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets

Songjian Lu, Kevin Lu, Shi-Yuan Cheng, Bo Hu, Xiaojun Ma, Nicholas Nystrom, Xinghua Lu

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

An important goal of cancer genomic research is to identify the driving pathways underlying disease mechanisms. It is well known that somatic genome alterations (SGAs) affecting the genes that encode the proteins within a common signaling pathway exhibit mutual exclusivity, in which these SGAs usually do not co-occur in a tumor. With some success, this property has been utilized as an objective function to guide the search for driver mutations. However, the mutual exclusivity alone is not sufficient to indicate that genes affected by such SGAs are in common pathways. Here, we propose a novel, signal-oriented framework for identifying driver SGAs, such that our new method constrains the mutual exclusivity only on tumors that have SGAs to perturb a common signal (not on all tumors as previous methods used). We apply this framework to the OV and GBM data FROM TCGA, and perform systematic evaluations. Our results indicate that the signal-oriented approach enhances the ability to find informative sets of driver SGAs that likely constitute signaling pathways.

Original languageEnglish (US)
Title of host publicationProceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
Editorslng. Matthieu Schapranow, Jiayu Zhou, Xiaohua Tony Hu, Bin Ma, Sanguthevar Rajasekaran, Satoru Miyano, Illhoi Yoo, Brian Pierce, Amarda Shehu, Vijay K. Gombar, Brian Chen, Vinay Pai, Jun Huan
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages1728-1730
Number of pages3
ISBN (Electronic)9781467367981
DOIs
StatePublished - Dec 16 2015
EventIEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015 - Washington, United States
Duration: Nov 9 2015Nov 12 2015

Publication series

NameProceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015

Other

OtherIEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015
CountryUnited States
CityWashington
Period11/9/1511/12/15

Fingerprint

Genes
Genome
Weights and Measures
Neoplasms
Tumors
Mutation
Proteins
Research

Keywords

  • formatting
  • insert
  • style
  • styling

ASJC Scopus subject areas

  • Software
  • Artificial Intelligence
  • Health Informatics
  • Biomedical Engineering

Cite this

Lu, S., Lu, K., Cheng, S-Y., Hu, B., Ma, X., Nystrom, N., & Lu, X. (2015). Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets. In L. M. Schapranow, J. Zhou, X. T. Hu, B. Ma, S. Rajasekaran, S. Miyano, I. Yoo, B. Pierce, A. Shehu, V. K. Gombar, B. Chen, V. Pai, ... J. Huan (Eds.), Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015 (pp. 1728-1730). [7359942] (Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015). Institute of Electrical and Electronics Engineers Inc.. https://doi.org/10.1109/BIBM.2015.7359942
Lu, Songjian ; Lu, Kevin ; Cheng, Shi-Yuan ; Hu, Bo ; Ma, Xiaojun ; Nystrom, Nicholas ; Lu, Xinghua. / Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets. Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015. editor / lng. Matthieu Schapranow ; Jiayu Zhou ; Xiaohua Tony Hu ; Bin Ma ; Sanguthevar Rajasekaran ; Satoru Miyano ; Illhoi Yoo ; Brian Pierce ; Amarda Shehu ; Vijay K. Gombar ; Brian Chen ; Vinay Pai ; Jun Huan. Institute of Electrical and Electronics Engineers Inc., 2015. pp. 1728-1730 (Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015).
@inproceedings{e069a69be80a44f1b4b4d9fcdac99089,
title = "Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets",
abstract = "An important goal of cancer genomic research is to identify the driving pathways underlying disease mechanisms. It is well known that somatic genome alterations (SGAs) affecting the genes that encode the proteins within a common signaling pathway exhibit mutual exclusivity, in which these SGAs usually do not co-occur in a tumor. With some success, this property has been utilized as an objective function to guide the search for driver mutations. However, the mutual exclusivity alone is not sufficient to indicate that genes affected by such SGAs are in common pathways. Here, we propose a novel, signal-oriented framework for identifying driver SGAs, such that our new method constrains the mutual exclusivity only on tumors that have SGAs to perturb a common signal (not on all tumors as previous methods used). We apply this framework to the OV and GBM data FROM TCGA, and perform systematic evaluations. Our results indicate that the signal-oriented approach enhances the ability to find informative sets of driver SGAs that likely constitute signaling pathways.",
keywords = "formatting, insert, style, styling",
author = "Songjian Lu and Kevin Lu and Shi-Yuan Cheng and Bo Hu and Xiaojun Ma and Nicholas Nystrom and Xinghua Lu",
year = "2015",
month = "12",
day = "16",
doi = "10.1109/BIBM.2015.7359942",
language = "English (US)",
series = "Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015",
publisher = "Institute of Electrical and Electronics Engineers Inc.",
pages = "1728--1730",
editor = "Schapranow, {lng. Matthieu} and Jiayu Zhou and Hu, {Xiaohua Tony} and Bin Ma and Sanguthevar Rajasekaran and Satoru Miyano and Illhoi Yoo and Brian Pierce and Amarda Shehu and Gombar, {Vijay K.} and Brian Chen and Vinay Pai and Jun Huan",
booktitle = "Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015",
address = "United States",

}

Lu, S, Lu, K, Cheng, S-Y, Hu, B, Ma, X, Nystrom, N & Lu, X 2015, Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets. in LM Schapranow, J Zhou, XT Hu, B Ma, S Rajasekaran, S Miyano, I Yoo, B Pierce, A Shehu, VK Gombar, B Chen, V Pai & J Huan (eds), Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015., 7359942, Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015, Institute of Electrical and Electronics Engineers Inc., pp. 1728-1730, IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015, Washington, United States, 11/9/15. https://doi.org/10.1109/BIBM.2015.7359942

Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets. / Lu, Songjian; Lu, Kevin; Cheng, Shi-Yuan; Hu, Bo; Ma, Xiaojun; Nystrom, Nicholas; Lu, Xinghua.

Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015. ed. / lng. Matthieu Schapranow; Jiayu Zhou; Xiaohua Tony Hu; Bin Ma; Sanguthevar Rajasekaran; Satoru Miyano; Illhoi Yoo; Brian Pierce; Amarda Shehu; Vijay K. Gombar; Brian Chen; Vinay Pai; Jun Huan. Institute of Electrical and Electronics Engineers Inc., 2015. p. 1728-1730 7359942 (Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015).

Research output: Chapter in Book/Report/Conference proceedingConference contribution

TY - GEN

T1 - Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets

AU - Lu, Songjian

AU - Lu, Kevin

AU - Cheng, Shi-Yuan

AU - Hu, Bo

AU - Ma, Xiaojun

AU - Nystrom, Nicholas

AU - Lu, Xinghua

PY - 2015/12/16

Y1 - 2015/12/16

N2 - An important goal of cancer genomic research is to identify the driving pathways underlying disease mechanisms. It is well known that somatic genome alterations (SGAs) affecting the genes that encode the proteins within a common signaling pathway exhibit mutual exclusivity, in which these SGAs usually do not co-occur in a tumor. With some success, this property has been utilized as an objective function to guide the search for driver mutations. However, the mutual exclusivity alone is not sufficient to indicate that genes affected by such SGAs are in common pathways. Here, we propose a novel, signal-oriented framework for identifying driver SGAs, such that our new method constrains the mutual exclusivity only on tumors that have SGAs to perturb a common signal (not on all tumors as previous methods used). We apply this framework to the OV and GBM data FROM TCGA, and perform systematic evaluations. Our results indicate that the signal-oriented approach enhances the ability to find informative sets of driver SGAs that likely constitute signaling pathways.

AB - An important goal of cancer genomic research is to identify the driving pathways underlying disease mechanisms. It is well known that somatic genome alterations (SGAs) affecting the genes that encode the proteins within a common signaling pathway exhibit mutual exclusivity, in which these SGAs usually do not co-occur in a tumor. With some success, this property has been utilized as an objective function to guide the search for driver mutations. However, the mutual exclusivity alone is not sufficient to indicate that genes affected by such SGAs are in common pathways. Here, we propose a novel, signal-oriented framework for identifying driver SGAs, such that our new method constrains the mutual exclusivity only on tumors that have SGAs to perturb a common signal (not on all tumors as previous methods used). We apply this framework to the OV and GBM data FROM TCGA, and perform systematic evaluations. Our results indicate that the signal-oriented approach enhances the ability to find informative sets of driver SGAs that likely constitute signaling pathways.

KW - formatting

KW - insert

KW - style

KW - styling

UR - http://www.scopus.com/inward/record.url?scp=84962343497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962343497&partnerID=8YFLogxK

U2 - 10.1109/BIBM.2015.7359942

DO - 10.1109/BIBM.2015.7359942

M3 - Conference contribution

AN - SCOPUS:84962343497

T3 - Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015

SP - 1728

EP - 1730

BT - Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015

A2 - Schapranow, lng. Matthieu

A2 - Zhou, Jiayu

A2 - Hu, Xiaohua Tony

A2 - Ma, Bin

A2 - Rajasekaran, Sanguthevar

A2 - Miyano, Satoru

A2 - Yoo, Illhoi

A2 - Pierce, Brian

A2 - Shehu, Amarda

A2 - Gombar, Vijay K.

A2 - Chen, Brian

A2 - Pai, Vinay

A2 - Huan, Jun

PB - Institute of Electrical and Electronics Engineers Inc.

ER -

Lu S, Lu K, Cheng S-Y, Hu B, Ma X, Nystrom N et al. Identifying driver genomic alterations in cancers by searching minimum-weight, mutually exclusive sets. In Schapranow LM, Zhou J, Hu XT, Ma B, Rajasekaran S, Miyano S, Yoo I, Pierce B, Shehu A, Gombar VK, Chen B, Pai V, Huan J, editors, Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015. Institute of Electrical and Electronics Engineers Inc. 2015. p. 1728-1730. 7359942. (Proceedings - 2015 IEEE International Conference on Bioinformatics and Biomedicine, BIBM 2015). https://doi.org/10.1109/BIBM.2015.7359942