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From Functional Genomics to Systems Biology

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From Functional Genomics to Systems Biology From Functional Genomics to Systems Biology Julio R. Fernández Masso Centro de Ingeniería Genética y Biotecnología. Ave 31 e/ 158 y 190, PO Box 6 162, Cubanacan, Cuba E-mail: [email protected] After the Transcriptome conferences held in Paris was presented by Mutsumi Kanamori from RIKEN. REPORT (2000), Seattle (2002), and Tokyo (2003), Prof. The comprehensive analysis of this cDNA collection Charles Auffray from the Centre National de la gave a great deal of information on the organization Recherche Scientifique (France), Pro. Zhu Chen, from of mammalian transcriptome. The project found an the Chinese Academy of Science and Chinese National unexpected number of alternative spliced transcripts Human Genome Research Centre (China) and Prof. and a significantly large amount of non coding RNAs Leroy Hood, from the Institute of Systems Biology (ncRNA). The expression analysis of a substantial (USA) launched a new series of conferences specially subset of predicted ncRNAs indicates that these designed to foster the transition of life science research RNAs are regulated in a tissue-specific manner and from Functional Genomics to Systems Biology. The that many of them may be involved in an antisense first of this new series of conferences was held in control mechanism. Their study concludes that Shanghai, China from November 5th to 9th 2005, under ncRNAs are a major component of the transcriptome. the topic of Integrative Systems Biology for Health- The following step they propose is the analysis of Predictive and Preventive Medicine. The conference expression regulatory regions, expression profiles and covers aspects such as Expression Profiling, RNAi, protein-RNA interactions, to unravel the Genome Proteomics, Metabolomics, Systems Biology on Network. Kanamori’s group established a large scale Model Organism, Systems Biology in Medicine, Systems to identify promoter regions and trans- Computation and Modeling and Integrative Annotation criptional starting sites. More than 10 million sites of the Genome. Conferences were presented by the were analyzed to discover new promoters and genes. academic and industrial sectors. From the combination of mapping full length cDNAs and promoter regions they identified low and high Understanding the genome activity chromosomal regions. The epigenetic interface between the genotype and One of the most surprising results of the human the phenotype links the genetic information and gene genome sequence is the scarcity of genes and the expression of an organism. The state of DNA vast tentions of meaningless genomic deserts, with methylation is the most widely studied epigenetic ultraconserved elements. Gustavo Glusman from the mechanism. A number of presentations expressed the Institute for Systems Biology proposes a novel importance of measuring the epigenetic changes as a approach to gene prediction. The new algorithms he measure of disease condition. Prototype techniques developed are based on the detection of genomic for the study of DNA methylation is a rapidly evolving signatures of transcription accumulated over field that should be closely followed since it will mature evolutionary time. He predicted thousands of rapidly in the scale of information and in performance. additional human genes including many that do not The relevance in tracking mutations in the genome code for proteins and genes with long introns and through the use of SNP or comparative genome lacking sequence conservation. He expects these new hybridatization to complement gene expression studies tools to add valuable information when combined in diseases that involve dynamic changes in the genome with algorithms based on gene structure and sequence such as cancer or mental retardation, and to understand similarity as a step forward in achieving the biological processes in stem cell research such as sensitivity and specificity required to fully automate pluripotence or cell differentiation, was pointed out. whole genome annotation. The complexity of the transcriptome Up and down regulated genes: from Full length cDNA sequence has been used to explore expression data to Biological the complexity of the transcriptome. Lukas Wagner meaning from NCBI presented the results obtained from One of the problems in microarray experiments is sequence 13000 human full length cDNA. While the that of developing tools to turn the data into coverage of alternative splicing was not a goal for the mechanistic understanding. The consensus at the project, the large number of EST and fully sequenced meeting was that most of the microarray papers cDNA provides an overview into the challenge of published in foremost journals still present a list of surveying splice variants. Sumio Sugano from the up and down regulated genes, the validation of certain University of Tokio determined the 5´end of genes by Western blot or qPCR, and the formulation 1,145,855 cDNA isolated from 134 full length of new hypotheses on the biological significance of enriched cDNA libraries. They identified a large some of these findings, but lack a significant population of cDNA that code for small proteins, a contribution to new biological understanding. The large number of alternative splices and alternative challenge in microarray studies has moved from the promoters. FANTOM3: The comprehensive mouse generation of high quality data sets to their analysis full length cDNA collection and seque nce database and interpretation. 144 Reportes Reports Xuegong Zhang from Tsinghua University presents genes could be deleterious for cells or could produce a subject-oriented literature mining tool developed in side effect on animals. Jacques Mallet from CNRS his lab for combining the information found in the presented a novel polymerase promoter inducible by literature with microarray gene expression data to doxycycline minimal RNA III that permits the control construct reliable and manageable gene networks with of siRNA levels and RNA interference by induction specific biological processes. The comparison and activation. possible advantages over other available tools was The Taicor method as a tool in the use of moderate discussed. RNAi screens to discover genes that are differentially Several talks refered to the importance of the regulated between cell lines was presented by Anyndya combination of microarray studies with other Dutta from the Univ. of Virginia Health Sciences technologies as CHIP to chip to increase the confidence Center. Using this technology it was possible to of gene expression studies and to allow the definition identify genes that are essential for cell cycle of gene and protein regulatory networks. Technical progression in p53+ cells but dispensable in p53- cells. advances in the field of microarray design for the genome, CHIP to chip and gene expression studies Annotation, data integration, and were presented during the meeting by Affymetrix and mining Agilent Technologies. Sequenom presented the data The process of genome annotation and the integration obtained from several papers using automated mass of different types of information generated by the spectrometry for gene expression and promoter use of high throughput technologies are challenges of methylation studies. today’s biological sciences. Several approaches such as H-invitational and Gene Desk databases and data The Proteome and the Metabolome integration tools such as BioMart were presented at Few presentations at the meeting cover the use of the meeting. Nevertheless the importance of proteomic or metabolomic tools. Nevertheless, it was developing new concepts, theories, computational clear that the understanding of the proteome and its and mathematical tools to explore and identify integration with transcriptome, the phosphorylation relevant interactions and networks was acknowledged profile and a network of protein-protein interactions by the participants. clearly provide a strong insight on mechanisms of biological Systemss. Mark McDonald from Waters Systems Biology described a new label free method for quantitative The concept of Systems Biology was used at the protein profiling that is based on the LC-MS conference at different scales of biological complexity: methodology that makes it possible to determine relative from metabolic pathways to cells and model changes in the amount of peptides in complex digest organisms. Charles Auffrey presented the Systemos- mixtures. The combination of chromatographic cope Consortium and his vision of Systems Biology separation and mass accuracy enables the identification as an integrational and iterative process based on inter- of thousands of ions. The SCAPE method based on the disciplinarity and networking. He proposed a working selective capture of peptides using chromatographic hypothesis that self organization of living systems separation was presented by Gabriel Padrón from CIGB. result from the conjunction of a stable organization This technology simplifies complex mixtures of proteins and chaotic fluctuations. Dr. Auffrey recognized the for their identification in proteome analysis. need to measure small variations of a large number of The expression of open reading frames is of special weak signals with high throughput technologies value to facilitate functional studies at the proteome developed under quality assurance. To achieve the level and to establish the biochemical and biophysical understanding of biological systems and stimulate properties of individual proteins and their molecular applications on preventive and predictive
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