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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