1 Genome Transcriptome Proteome Metabolome Genome: the complete - - PDF document

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Proteomics

PROTEOMICS PROTEOMICS: The analysis of the entire protein complement expressed by a genome, or by a cell or tissue type PROTEOMICS PROTEOMICS: The study of biological systems based on global knowledge of genomes, transcriptomes, proteomes, metabolomes

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Genome Genome: the complete set of hereditary material Genomics Genomics: size, content, qualities, gene prediction (2/ 3 identified genes have no known function!), comparative genomics, one context of gene expression, …

Genome Transcriptome Proteome Metabolome

Transcriptome Transcriptome: complete set of gene transcripts, transcriptional modifications, patterns of expression, mechanisms of regulation. Tramscriptomincs: systems of regulation and co-regulation, comparative analysis of expression patterns, relation to functional genomics, …

Genome Transcriptome Proteome Metabolome

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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)

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Transcriptom ics

• Trascriptomics studies processes at genome-wide scale
• Genome ⇒ DNA-microarray ⇒ mRNA level of all genes in

genome

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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 Proteome Proteome: Complete set of proteins, structures, post- translational modifications, localizations Proteomics Proteomics: Study of the above as a complex system

Genome Transcriptome Proteome Metabolome

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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? > 106 ? 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.

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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

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Is there a relationship between alternative splicing and mixing and matching modules?

Kriventseva et al (2003) TIG 19:124-128

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

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Metabolome Metabolome: Complete set of metabolites, concentrations, and contextual metabolic pathways Metabolomics Metabolomics: : Study of the above as a complex interacting system. Genome Transcriptome Proteome Metabolome

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

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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.