Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues

Motivation Global protein interaction network (interactome) analysis provides an effective way to understand the relationships between genes. Through this approach, it was demonstrated that the essential genes in yeast tend to be highly connected as well as connected to other highly connected genes. This is in contrast to the genes that are not essential, which share neither of these properties. Using a similar interactome-transcriptome approach, the topological features in the interactome of differentially expressed genes in lung squamous cancer tissues are assessed. Results This analysis reveals that the genes that are differentially elevated, as obtained from the microarray gene profiling data, in cancer are well connected, whereas the suppressed genes and randomly selected ones are less so. These results support the notion that a topological analysis of cancer genes using protein interaction data will allow the placement of the list of genes, often of the disparate nature, into the global, systematic context of the cell. The result of this type of analysis may provide the rationale for therapeutic targets in cancer treatment.

[1]  A. Fraser,et al.  A first-draft human protein-interaction map , 2004, Genome Biology.

[2]  M. Vidal,et al.  Identification of potential interaction networks using sequence-based searches for conserved protein-protein interactions or "interologs". , 2001, Genome research.

[3]  John Quackenbush,et al.  Open source software for the analysis of microarray data. , 2003, BioTechniques.

[4]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[5]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[6]  Christian A. Rees,et al.  Molecular portraits of human breast tumours , 2000, Nature.

[7]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[8]  James R. Knight,et al.  A Protein Interaction Map of Drosophila melanogaster , 2003, Science.

[9]  Thomas J. Begley,et al.  Global network analysis of phenotypic effects: Protein networks and toxicity modulation in Saccharomyces cerevisiae , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Igor Jurisica,et al.  Online Predicted Human Interaction Database , 2005, Bioinform..

[11]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[12]  L. Penland,et al.  Use of a cDNA microarray to analyse gene expression patterns in human cancer , 1996, Nature Genetics.

[13]  J. John Mann,et al.  Sex genes for genomic analysis in human brain: internal controls for comparison of probe level data extraction. , 2003, BMC Bioinformatics.

[14]  Stefan Wuchty,et al.  Peeling the yeast protein network , 2005, Proteomics.

[15]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[16]  R. Karp,et al.  From the Cover : Conserved patterns of protein interaction in multiple species , 2005 .

[17]  T. Ideker,et al.  A new approach to decoding life: systems biology. , 2001, Annual review of genomics and human genetics.

[18]  T. Chiba,et al.  Exploring the protein interactome using comprehensive two-hybrid projects. , 2001, Trends in biotechnology.

[19]  S. L. Wong,et al.  A Map of the Interactome Network of the Metazoan C. elegans , 2004, Science.

[20]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[21]  D. Lockhart,et al.  Expression monitoring by hybridization to high-density oligonucleotide arrays , 1996, Nature Biotechnology.

[22]  A. Barabasi,et al.  Lethality and centrality in protein networks , 2001, Nature.

[23]  Ross Ihaka,et al.  Gentleman R: R: A language for data analysis and graphics , 1996 .

[24]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.

[25]  A. Mendelsohn,et al.  Protein Interaction Methods-Toward an Endgame , 1999, Science.

[26]  J. Claverie Computational methods for the identification of differential and coordinated gene expression. , 1999, Human molecular genetics.