| 1. |
- Barrenäs, Fredrik, et al.
(author)
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Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms
- 2012
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In: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X .- 1465-6914. ; 13:6, s. R46-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases.RESULTS: We identified modules of highly interconnected genes in disease-specific networks derived from integrating gene-expression and protein interaction data. We examined if those modules were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies. First, we analyzed publicly available gene expression microarray and genome-wide association study (GWAS) data from 13, highly diverse, complex diseases. In each disease, highly interconnected genes formed modules, which were significantly enriched for genes harboring disease-associated SNPs. To test if such modules could be used to find novel genes for functional studies, we repeated the analyses using our own gene expression microarray and GWAS data from seasonal allergic rhinitis. We identified a novel gene, FGF2, whose relevance was supported by functional studies using combined small interfering RNA-mediated knock-down and gene expression microarrays. The modules in the 13 complex diseases analyzed here tended to overlap and were enriched for pathways related to oncological, metabolic and inflammatory diseases. This suggested that this union of the modules would be associated with a general increase in susceptibility for complex diseases. Indeed, we found that this union was enriched with GWAS genes for 145 other complex diseases.CONCLUSIONS: Modules of highly interconnected complex disease genes were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies.
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| 2. |
- Gabaldón, Toni, et al.
(author)
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Joining forces in the quest for orthologs
- 2009
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In: Genome biology. - : Springer Science and Business Media LLC. - 1465-6914 .- 1465-6906. ; 10:9, s. 403-
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Journal article (peer-reviewed)abstract
- Better orthology-prediction resources would be beneficial for the whole biological community. A recent meeting discussed how to coordinate and leverage current efforts.
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| 3. |
- Juncker, Agnieszka S, et al.
(author)
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Sequence-based feature prediction and annotation of proteins
- 2009
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In: Genome biology. - : Springer Science and Business Media LLC. - 1465-6914 .- 1465-6906. ; 10:2, s. 206-
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Journal article (peer-reviewed)abstract
- A recent trend in computational methods for annotation of protein function is that many prediction tools are combined in complex workflows and pipelines to facilitate the analysis of feature combinations, for example, the entire repertoire of kinase-binding motifs in the human proteome.
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| 4. |
- Staaf, Johan, et al.
(author)
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Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arrays
- 2008
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1474-7596 .- 1465-6906 .- 1465-6914. ; 9:9
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Journal article (peer-reviewed)abstract
- We present a strategy for detection of loss-of-heterozygosity and allelic imbalance in cancer cells from whole genome single nucleotide polymorphism genotyping data. Using a dilution series of a tumor cell line mixed with its paired normal cell line and data generated on Affymetrix and Illumina platforms, including paired tumor-normal samples and tumors characterized by fluorescent in situ hybridization, we demonstrate a high sensitivity and specificity of the strategy for detecting both minute and gross allelic imbalances in heterogeneous tumor samples.
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| 5. |
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| 6. |
- Zou, Zhen, et al.
(author)
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Comparative genomic analysis of the Tribolium immune system.
- 2007
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In: Genome Biol. - 1465-6914. ; 8:8, s. R177.1-16
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Journal article (peer-reviewed)abstract
- BACKGROUND: Tribolium castaneum is a species of Coleoptera, the largest and most diverse order of all eukaryotes. Components of the innate immune system are hardly known in this insect, which is in a key phylogenetic position to inform us about genetic innovations accompanying the evolution of holometabolous insects. We have annotated immunity-related genes and compared them with homologous molecules from other species. RESULTS: Around 300 candidate defense proteins are identified based on sequence similarity to homologs known to participate in immune responses. In most cases, paralog counts are lower than those of Drosophila melanogaster or Anopheles gambiae but are substantially higher than Apis mellifera. The genome contains probable orthologs for nearly all members of the Toll, IMD, and JAK/STAT pathways. While total numbers of the clip-domain serine proteinases are approximately equal in the fly (29), mosquito (32) and beetle (30), lineage-specific expansion of the family is discovered in all three species. Sixteen of the thirty-one serpin genes form a large cluster in a 50 kb region resulted from extensive gene duplications. Among the nine Toll-like proteins, four are orthologous to Drosophila Toll. The presence of scavenger receptors and other related proteins indicates a role of cellular responses in the entire system. The structures of some antimicrobial peptides drastically differ from those in other orders of insects. CONCLUSIONS: A framework of information on Tribolium immunity is established, which may serve as a stepping stone for future genetic analyses of defense responses in a nondrosophiline genetic model insect.
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