@article {19246752,
	title = {Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli},
	journal = {Microbiology},
	volume = {155},
	number = {Pt 3},
	year = {2009},
	note = {<p>Nobre, Ligia S Al-Shahrour, Fatima Dopazo, Joaquin Saraiva, Ligia M Research Support, Non-U.S. Gov{\textquoteright}t England Microbiology (Reading, England) Microbiology. 2009 Mar;155(Pt 3):813-24.</p>},
	pages = {813-24},
	abstract = {<p>We recently reported that carbon monoxide (CO) has bactericidal activity. To understand its mode of action we analysed the gene expression changes occurring when Escherichia coli, grown aerobically and anaerobically, is treated with the CO-releasing molecule CORM-2 (tricarbonyldichlororuthenium(II) dimer). Microarray analysis shows that the E. coli CORM-2 response is multifaceted, with a high number of differentially regulated genes spread through several functional categories, namely genes involved in inorganic ion transport and metabolism, regulators, and genes implicated in post-translational modification, such as chaperones. CORM-2 has a higher impact in E. coli cells grown anaerobically, as judged by the repression of genes belonging to eight functional classes which are not seen in the response of aerobically CORM-2-treated cells. The biological relevance of the variations caused by CORM-2 was substantiated by studying the CORM-2 sensitivity of selected E. coli mutants. The results show that the deletion of redox-sensing regulators SoxS and OxyR increased the sensitivity to CORM-2 and suggest that while SoxS plays an important role in protection against CORM-2 under both growth conditions, OxyR seems to participate only in the aerobic CORM-2 response. Under anaerobic conditions, we found that the heat-shock proteins IbpA and IbpB contribute to CORM-2 defence since the deletion of these genes increases the sensitivity of the strain. The induction of several met genes and the hypersensitivity to CORM-2 of the DeltametR, DeltametI and DeltametN mutant strains suggest that CO has effects on the methionine metabolism of E. coli. CORM-2 also affects the transcription of several E. coli biofilm-related genes and increases biofilm formation in E. coli. In particular, the absence of tqsA or bhsA increases the resistance of E. coli to CORM-2, and deletion of tsqA leads to a strain that has lost its capacity to form biofilm upon treatment with CORM-2. In spite of the relatively stable nature of the CO molecule, our results show that CO is able to trigger a significant alteration in the transcriptome of E. coli which necessarily has effects in several key metabolic pathways.</p>},
	keywords = {Bacterial Genes, Bacterial/genetics, Biofilms Carbon Monoxide/*metabolism Escherichia coli/*genetics/metabolism Escherichia coli Proteins/genetics/metabolism *Gene Expression Profiling Gene Expression Regulation, Regulator Genetic Complementation Test Methionine/metabolism Microbial Viability Mutation Oligonucleotide Array Sequence Analysis Organometallic Compounds/*pharmacology Phenotype RNA},
	url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\&db=PubMed\&dopt=Citation\&list_uids=19246752},
	author = {Nobre, L. S. and Fatima Al-Shahrour and Dopazo, J. and Saraiva, L. M.}
}
@article {17584915,
	title = {Evidence for systems-level molecular mechanisms of tumorigenesis},
	journal = {BMC Genomics},
	volume = {8},
	year = {2007},
	note = {Hernandez, Pilar Huerta-Cepas, Jaime Montaner, David Al-Shahrour, Fatima Valls, Joan Gomez, Laia Capella, Gabriel Dopazo, Joaquin Pujana, Miguel Angel Research Support, Non-U.S. Gov{\textquoteright}t England BMC genomics BMC Genomics. 2007 Jun 20;8:185.},
	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, Biological Models, Genetic Models, Messenger/metabolism Signal Transduction Systems Biology, Neoplastic *Gene Expression Profiling *Gene Expression Regulation, Neoplastic Humans Male Models, Statistical Neoplasm Proteins/*physiology Neoplasms/etiology/*genetics Prostatic Neoplasms/genetics Protein Interaction Mapping RNA},
	url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\&db=PubMed\&dopt=Citation\&list_uids=17584915},
	author = {Hernandez, P. and Huerta-Cepas, J. and Montaner, D. and Fatima Al-Shahrour and Valls, J. and Gomez, L. and Capella, G. and Dopazo, J. and Pujana, M. A.}
}
@article {17018596,
	title = {ERCC4 associated with breast cancer risk: a two-stage case-control study using high-throughput genotyping},
	journal = {Cancer Res},
	volume = {66},
	number = {19},
	year = {2006},
	note = {Milne, Roger Laughlin Ribas, Gloria Gonzalez-Neira, Anna Fagerholm, Rainer Salas, Antonio Gonzalez, Emilio Dopazo, Joaquin Nevanlinna, Heli Robledo, Mercedes Benitez, Javier Comparative Study Multicenter Study Research Support, Non-U.S. Gov{\textquoteright}t United States Cancer research Cancer Res. 2006 Oct 1;66(19):9420-7.},
	pages = {9420-7},
	abstract = {The failure of linkage studies to identify further high-penetrance susceptibility genes for breast cancer points to a polygenic model, with more common variants having modest effects on risk, as the most likely candidate. We have carried out a two-stage case-control study in two European populations to identify low-penetrance genes for breast cancer using high-throughput genotyping. Single-nucleotide polymorphisms (SNPs) were selected across preselected cancer-related genes, choosing tagSNPs and functional variants where possible. In stage 1, genotype frequencies for 640 SNPs in 111 genes were compared between 864 breast cancer cases and 845 controls from the Spanish population. In stage 2, candidate SNPs identified in stage 1 (nominal P < 0.01) were tested in a Finnish series of 884 cases and 1,104 controls. Of the 10 candidate SNPs in seven genes identified in stage 1, one (rs744154) on intron 1 of ERCC4, a gene belonging to the nucleotide excision repair pathway, was associated with recessive protection from breast cancer after adjustment for multiple testing in stage 2 (odds ratio, 0.57; Bonferroni-adjusted P = 0.04). After considering potential functional SNPs in the region of high linkage disequilibrium that extends across the entire gene and upstream into the promoter region, we concluded that rs744154 itself could be causal. Although intronic, it is located on the first intron, in a region that is highly conserved across species, and could therefore be functionally important. This study suggests that common intronic variation in ERCC4 is associated with protection from breast cancer.},
	keywords = {80 and over Breast Neoplasms/epidemiology/*genetics/pathology Case-Control Studies DNA-Binding Proteins/genetics/*physiology Female Finland/epidemiology Genes, Adult Aged Aged, Recessive Genetic Predisposition to Disease Genotype Humans Introns/genetics Linkage Disequilibrium Middle Aged Neoplasm Proteins/genetics/*physiology Neoplasm Staging *Polymorphism, Single Nucleotide Risk Spain/epidemiology},
	url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\&db=PubMed\&dopt=Citation\&list_uids=17018596},
	author = {Milne, R. L. and Ribas, G. and Gonzalez-Neira, A. and Fagerholm, R. and Salas, A. and Gonzalez, E. and Dopazo, J. and Nevanlinna, H. and M. Robledo and Benitez, J.}
}
@article {16566817,
	title = {Exploring the reasons for the large density of triplex-forming oligonucleotide target sequences in the human regulatory regions},
	journal = {BMC Genomics},
	volume = {7},
	year = {2006},
	note = {Goni, Josep Ramon Vaquerizas, Juan Manuel Dopazo, Joaquin Orozco, Modesto Research Support, Non-U.S. Gov{\textquoteright}t England BMC genomics BMC Genomics. 2006 Mar 27;7:63.},
	pages = {63},
	abstract = {BACKGROUND: DNA duplex sequences that can be targets for triplex formation are highly over-represented in the human genome, especially in regulatory regions. RESULTS: Here we studied using bioinformatics tools several properties of triplex target sequences in an attempt to determine those that make these sequences so special in the genome. CONCLUSION: Our results strongly suggest that the unique physical properties of these sequences make them particularly suitable as "separators" between protein-recognition sites in the promoter region.},
	keywords = {Animals Base Sequence Computational Biology DNA/chemistry/*genetics/*metabolism Genome, Genetic/genetics Regulatory Sequences, Human/genetics Humans Mice Nucleic Acid Conformation Nucleotides/genetics Oligonucleotides/chemistry/*genetics/*metabolism Promoter Regions, Nucleic Acid/*genetics Transcription Factors/metabolism},
	url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve\&db=PubMed\&dopt=Citation\&list_uids=16566817},
	author = {Goni, J. R. and Vaquerizas, J. M. and Dopazo, J. and Orozco, M.}
}
