From signatures to models: understanding cancer using microarrays

被引:261
作者
Segal, E
Friedman, N
Kaminski, N
Regev, A
Koller, D
机构
[1] Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10021 USA
[2] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA
[3] Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA
[4] Univ Pittsburgh, Pittsburgh, PA 15260 USA
[5] Hebrew Univ Jerusalem, Sch Engn & Comp Sci, Jerusalem, Israel
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
D O I
10.1038/ng1561
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Genomics has the potential to revolutionize the diagnosis and management of cancer by offering an unprecedented comprehensive view of the molecular underpinnings of pathology. Computational analysis is essential to transform the masses of generated data into a mechanistic understanding of disease. Here we review current research aimed at uncovering the modular organization and function of transcriptional networks and responses in cancer. We first describe how methods that analyze biological processes in terms of higher-level modules can identify robust signatures of disease mechanisms. We then discuss methods that aim to identify the regulatory mechanisms underlying these modules and processes. Finally, we show how comparative analysis, combining human data with model organisms, can lead to more robust findings. We conclude by discussing the challenges of generalizing these methods from cells to tissues and the opportunities they offer to improve cancer diagnosis and management.
引用
收藏
页码:S38 / S45
页数:8
相关论文
共 70 条
[51]   Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression [J].
Rhodes, DR ;
Yu, JJ ;
Shanker, K ;
Deshpande, N ;
Varambally, R ;
Ghosh, D ;
Barrette, T ;
Pandey, A ;
Chinnaiyan, AM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (25) :9309-9314
[52]   Assigning numbers to the arrows: Parameterizing a gene regulation network by using accurate expression kinetics [J].
Ronen, M ;
Rosenberg, R ;
Shraiman, BI ;
Alon, U .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) :10555-10560
[53]  
Rostomily RC, 1997, CANCER RES, V57, P3526
[54]   Transcriptional control in the segmentation gene network of Drosophila [J].
Schroeder, MD ;
Pearce, M ;
Fak, J ;
Fan, HQ ;
Unnerstall, U ;
Emberly, E ;
Rajewsky, N ;
Siggia, ED ;
Gaul, U .
PLOS BIOLOGY, 2004, 2 (09) :1396-1410
[55]   Genome-wide discovery of transcriptional modules from DNA sequence and gene expression [J].
Segal, E. ;
Yelensky, R. ;
Koller, D. .
BIOINFORMATICS, 2003, 19 :i273-i282
[56]   A module map showing conditional activity of expression modules in cancer [J].
Segal, E ;
Friedman, N ;
Koller, D ;
Regev, A .
NATURE GENETICS, 2004, 36 (10) :1090-1098
[57]   Module networks: identifying regulatory modules and their condition-specific regulators from gene expression data [J].
Segal, E ;
Shapira, M ;
Regev, A ;
Pe'er, D ;
Botstein, D ;
Koller, D ;
Friedman, N .
NATURE GENETICS, 2003, 34 (02) :166-176
[58]  
SEGAL E, 2004, RECOMB 2004 P 8 ANN, P141
[59]  
SEGAL E, 2002, P 6 INT C RES COMP M, P263
[60]   CREME:: Cis-Regulatory Module Explorer for the human genome [J].
Sharan, R ;
Ben-Hur, A ;
Loots, GG ;
Ovcharenko, I .
NUCLEIC ACIDS RESEARCH, 2004, 32 :W253-W256