@article {604, title = {Evidence for systems-level molecular mechanisms of tumorigenesis.}, journal = {BMC Genomics}, volume = {8}, year = {2007}, month = {2007 Jun 20}, pages = {185}, abstract = {

BACKGROUND: Cancer arises from the consecutive acquisition of genetic alterations. Increasing evidence suggests that as a consequence of these alterations, molecular interactions are reprogrammed in the context of highly connected and regulated cellular networks. Coordinated reprogramming would allow the cell to acquire the capabilities for malignant growth.

RESULTS: Here, we determine the coordinated function of cancer gene products (i.e., proteins encoded by differentially expressed genes in tumors relative to healthy tissue counterparts, hereafter referred to as "CGPs") defined as their topological properties and organization in the interactome network. We show that CGPs are central to information exchange and propagation and that they are specifically organized to promote tumorigenesis. Centrality is identified by both local (degree) and global (betweenness and closeness) measures, and systematically appears in down-regulated CGPs. Up-regulated CGPs do not consistently exhibit centrality, but both types of cancer products determine the overall integrity of the network structure. In addition to centrality, down-regulated CGPs show topological association that correlates with common biological processes and pathways involved in tumorigenesis.

CONCLUSION: Given the current limited coverage of the human interactome, this study proposes that tumorigenesis takes place in a specific and organized way at the molecular systems-level and suggests a model that comprises the precise down-regulation of groups of topologically-associated proteins involved in particular functions, orchestrated with the up-regulation of specific proteins.

}, keywords = {Cell Transformation, Neoplastic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Models, Biological, Models, Genetic, Models, Statistical, Neoplasm Proteins, Neoplasms, Prostatic Neoplasms, Protein Interaction Mapping, RNA, Messenger, Signal Transduction, Systems biology}, issn = {1471-2164}, doi = {10.1186/1471-2164-8-185}, author = {Hern{\'a}ndez, Pilar and Huerta-Cepas, Jaime and Montaner, David and Al-Shahrour, F{\'a}tima and Valls, Joan and G{\'o}mez, Laia and Capell{\`a}, Gabriel and Dopazo, Joaquin and Pujana, Miguel Angel} } @article {608, title = {ISACGH: a web-based environment for the analysis of Array CGH and gene expression which includes functional profiling.}, journal = {Nucleic Acids Res}, volume = {35}, year = {2007}, month = {2007 Jul}, pages = {W81-5}, abstract = {

We present the ISACGH, a web-based system that allows for the combination of genomic data with gene expression values and provides different options for functional profiling of the regions found. Several visualization options offer a convenient representation of the results. Different efficient methods for accurate estimation of genomic copy number from array-CGH hybridization data have been included in the program. Moreover, the connection to the gene expression analysis package GEPAS allows the use of different facilities for data pre-processing and analysis. A DAS server allows exporting the results to the Ensembl viewer where contextual genomic information can be obtained. The program is freely available at: http://isacgh.bioinfo.cipf.es or within http://www.gepas.org.

}, keywords = {Animals, Cluster Analysis, Computational Biology, Computer Graphics, Gene Expression Profiling, Humans, Internet, Models, Genetic, Nucleic Acid Hybridization, Oligonucleotide Array Sequence Analysis, Programming Languages, Software, Systems Integration, User-Computer Interface}, issn = {1362-4962}, doi = {10.1093/nar/gkm257}, author = {Conde, Lucia and Montaner, David and Burguet-Castell, Jordi and T{\'a}rraga, Joaqu{\'\i}n and Medina, Ignacio and Al-Shahrour, F{\'a}tima and Dopazo, Joaquin} }