Proteomics PROTEOMICS: The analysis of the entire protein PROTEOMICS complement expressed by a genome, or by a cell or tissue type PROTEOMICS: The study of biological systems based on PROTEOMICS global knowledge of genomes, transcriptomes, proteomes, metabolomes 1
Genome Transcriptome Proteome Metabolome Genome: the complete set of hereditary material Genome Genomics: size, content, qualities, gene prediction (2/ 3 Genomics identified genes have no known function!), comparative genomics, one context of gene expression, … Genome Transcriptome Proteome Metabolome Transcriptome: complete set of gene transcripts, Transcriptome transcriptional modifications, patterns of expression, mechanisms of regulation. Tramscriptomincs: systems of regulation and co-regulation, comparative analysis of expression patterns, relation to functional genomics, … 2
Transcriptom ics • Transcripts are link between genome and proteome • Transcriptome is intensely interesting to evolutionary biologists • Regulation of transcription is the key process for adaptation of an organism to changes in environmental conditions and survival • stress: flight or fight • infection: immune and other defense responses • environmental changes: hibernation and torpor • etc. Problem : RNA is very difficult to w ork w ith • mRNA transtripomics uses an enzyme called reverse trasncriptase to convert it to com plim entary DNA ( cDNA) • cDNA: (i) stable, and (ii) no introns! • EST: expressed sequence tag • EST is generated by sequencing from one of the ends of the cDNA (hence you can have 5’ ESTs or 3’ ESTs) 3
Transcriptom ics • Trascriptomics studies processes at genome-wide scale • Genome ⇒ DNA-microarray ⇒ mRNA level of all genes in genome 4
Transcriptom ics • Molecular genetics: Which genes are activated by a particular transcription factor? • Medical research: What are the characteristic patterns of gene expression in cancer cells? • Practical medicine: What are the characteristic patterns for different diseases? The patterns can then be used to screen for a particular disease • Evolutionary comparative biology: What are the differences in gene expression between human and chimps • Molecular ecology and evolution: What is difference in gene expression of the same species in different environment Genome Transcriptome Proteome Metabolome Proteome: Complete set of proteins, structures, post- Proteome translational modifications, localizations Proteomics: Study of the above as a complex system Proteomics 5
Proteomes are much much more complex than genomes • min 1 proteome per tissue type (250 tissue types in humans) • sub cellular fractions have different proteomes • proteomes respond to external influences (food, drugs, stress, etc.) • proteomes change in time and space How many proteomes per individual? > 10 6 ? Types of Proteomics • Protein Expression – Quantitative study of protein expression between samples that differ by some variable • Structural Proteomics – Goal is to map out the 3-D structure of proteins and protein complexes • Functional Proteomics – To study protein-protein interaction, 3-D structures, cellular localization, interactions with DNA, RNA, and other chemicals (ligands, co-factors, etc.) to understand the functions of proteins and interacting sets of proteins. 6
Remember alternative splicing ‘- omics ’ and molecule evolution: alternative splicing Before ‘omics’: Alternatively spliced genes ~ 5% After ` omics’: Alternatively spliced genes from 40% -60% . Finding alt. Splicing by: • Aligning ESTs/ cDNAs to Genomic DNA • Aligning ESTs/ cDNAs to expressed proteins • Aligning ESTs/ cDNAa to (presumably) introns 7
Is there a relationship between alternative splicing and mixing and matching modules? 1. Insertion and deletion of complete modules occurs more frequently than expected by chance 2. Disruption of modules occurs less frequently than expected by chance Kriventseva et al (2003) TIG 19:124-128 8
Genome Transcriptome Proteome Metabolome Metabolome: Complete set of metabolites, concentrations, and Metabolome contextual metabolic pathways Metabolomics: : Study of the above as a complex interacting Metabolomics system. Metaboloimcs: • Metabolites are the end products of gene expression • Metabolomics provides a way of looking at genes as part of a functional system (signaling, regulation, etc.) • Metabolome represents a new way of measuring the phenotype of a cell or an organism. Exciting but extremely complex and challenging 9
Systems Biology (even more challenging): • ( genomics + transcriptomics + protomics + metabolomics) • view these data as a network that results from system • model the system by trying to infer the paths of the network and the linear and nonlinear correlations of the components of the system. • components need not be individual elements of the system; they can take the form of subsystems of different sizes that interact with other such subsystems at different levels Systems biology correlation network for selected gene products, lipoprteins, and lipids. 10
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