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Transcript
Institute for Animal Health
Comparative analyses
Institute for Animal Health
Research at the IAH
• Infectious diseases of farm animals
– Chicken
• Salmonella
• Eimeria (coccidiosis)
• Marek’s disease
– Cow
• Foot and Mouth
• Pestivirus
• Streptococcal infection (mastitis)
– Pig
• African Swine Fever
• Foot and Mouth
– Sheep
• TSEs (scrapie)
• Orbivirus
Institute for Animal Health
Host-Pathogen Interactions
Typical Problem
Comparative
Genomics
Gene Expression
Analysis
Related species – different
phenotype (hostspecificity/pathogenicity)
Proteomic Analysis
Institute for Animal Health
Genomics
• Bacterial
– Gene location, structure and function
• Up to 25,000 misannotated genes by comparative analysis
– Pathways, secreted proteins, interaction with host
• Chicken/Cow
– Identification of orthologues and paralogues
– Functional annotation poor
• Eimeria
– Unassembled genome
– Other related genomes poorly annotated too
– Related genomes are largely unspliced, Eimeria is spliced
Institute for Animal Health
Genomics
• Comparative genomics
– Chicken vs Human
• Bacterial
Institute for Animal Health
Kaiser P, Poh T-y, Rothwell L, Avery S, Balu S, Pathania U, Hughes S,
Goodchild M, Morrell S, Watson M, Bumstead N, Kaufman J, Young J
(2005) A genomic analysis of chicken cytokines and chemokines. J
Interferon and Chemokine Research, 25:467–484
Current Strategy - Research
• Comparative genomics
– At sequence level, reveals genome organisation
• Comparative genomics
– Also reveals function
– Kegg
•
•
•
•
Human: 159
Mouse: 155
Chicken: 31
Cow: 12
Institute for Animal Health
– Transfac
•
•
•
•
Human: 1041
Mouse: 765
Chicken: 200
Cow: 10
Transcriptomics
• Overlay gene expression data on functional annotation
– GO categories
– Pathways
– Interactions networks
• Problem: the relationship of RNA abundance to protein abundance
is not straight forward
– Post-transcriptional regulation
• siRNA, miRNA
– Post-translational regulation
• Protein phosphrylation
• Protein complexes
• When interpreting gene expression data in terms of the actions of
proteins, we must consider models that include all of the above
Institute for Animal Health
Transcriptomics
Data Exploration
Normalisation
• Salmonella infection
Institute for Animal Health
Differential
Expression
Patterns of Gene
Expression
Proteomics
• Mass Spec data
– Peptide -> protein -> function?
• Source of protein search library is often the genome…
• Lack of functional annotation of genomes of interest
• Link to microarray data
– Through genome
– Protein -> peptide -> gene
Institute for Animal Health
Keywords
• Genome, proteome, transcriptome
• Gene, protein, peptide, transcript, promoter,
regulator, transcription factor, miRNA, siRNA,
enzyme etc
• Interaction, pathway, network
• Orthologue, paralogue, homologue
• Microarray data, sequence data, mass spec
data
• Package, software, method, p-value
Institute for Animal Health