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Gene signature-based mapping of immunological systems and diseases.

Liu H, Liu J, Toups M, Soos T, Arendt C - BMC Bioinformatics (2016)

Bottom Line: An in silico approach has been developed to characterize immune cell subsets and diseases based on the gene signatures that most differentiate them from other biological states.This modular 'biomap' reveals the linkages between different diseases and immune subtypes, and provides evidence for the presence of specific immunocyte subsets in mixed tissues.The over-represented genes in disease signatures of interest can be further investigated for their functions in both host defense and disease.

View Article: PubMed Central - PubMed

Affiliation: Bio-Innovation, Sanofi Global Biotherapeutics, 38 Sidney Street, Cambridge, MA, 02139, USA. hong.liu@sanofi.com.

ABSTRACT

Background: The immune system is multifaceted, structured by diverse components that interconnect using multilayered dynamic cellular processes. Genomic technologies provide a means for investigating, at the molecular level, the adaptations of the immune system in host defense and its dysregulation in pathological conditions. A critical aspect of intersecting and investigating complex datasets is determining how to best integrate genomic data from diverse platforms and heterogeneous sample populations to capture immunological signatures in health and disease.

Result: We focus on gene signatures, representing highly enriched genes of immune cell subsets from both diseased and healthy tissues. From these, we construct a series of biomaps that illustrate the molecular linkages between cell subsets from different lineages, the connectivity between different immunological diseases, and the enrichment of cell subset signatures in diseased tissues. Finally, we overlay the downstream genes of drug targets with disease gene signatures to display the potential therapeutic applications for these approaches.

Conclusion: An in silico approach has been developed to characterize immune cell subsets and diseases based on the gene signatures that most differentiate them from other biological states. This modular 'biomap' reveals the linkages between different diseases and immune subtypes, and provides evidence for the presence of specific immunocyte subsets in mixed tissues. The over-represented genes in disease signatures of interest can be further investigated for their functions in both host defense and disease.

No MeSH data available.


Related in: MedlinePlus

Topological localization of drug target genes and signature disease genes. (I) Network-based separation scores of IL17A target genes and signature disease genes of different disease categories. (II) Network connection of IL17A target genes and IBD signature disease genes. Line represents the direct link between the two groups. Green color: IL17A target gene; blue color: IBD signature disease gene; orange color: common gene. Green color with red outline: target genes have direct connection with more than six signature disease genes
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Fig8: Topological localization of drug target genes and signature disease genes. (I) Network-based separation scores of IL17A target genes and signature disease genes of different disease categories. (II) Network connection of IL17A target genes and IBD signature disease genes. Line represents the direct link between the two groups. Green color: IL17A target gene; blue color: IBD signature disease gene; orange color: common gene. Green color with red outline: target genes have direct connection with more than six signature disease genes

Mentions: In addition to evaluating the direct gene overlap between drug target and disease signatures, we can also assess the topological distribution of drug target genes and signature disease genes on the interactome. As an example, we calculated the network-based separation score of IL17A target genes and signature disease genes of different disease categories. IL17A plays a pivotal role in psoriasis pathogenesis, and its antagonists show great efficacy in moderate-severe psoriasis patients. Shown in Fig. 8I, the negative separation score indicates that IL17A target genes and psoriasis signature disease genes share overlapping ‘neighborhoods’ and are positioned closely on the interactome. In addition to psoriasis, IL17A target genes also show close relatedness with signature disease genes of other indications, such as IBD, COPD, dermatitis, lupus, and arthritis. To explore the connection between IL17A target genes and IBD signature disease genes, the pair with the lowest separation score, we depict the direct links between the two gene sets on the interactome (Fig. 8II). A total of 148 IL17A target genes and 79 IBD signature disease genes can be mapped to the interactome, including 19 genes in common. Out of the 129 IL17A target-specific genes, 87 have a direct connection with at least one signature disease gene of IBD. Among these, 11 genes (circled in red) have connections with more than six signature disease genes. The close connection of target genes and signature disease genes suggests that the alteration of target genes with drug intervention may potentially have a direct impact on those signature disease genes.Fig. 8


Gene signature-based mapping of immunological systems and diseases.

Liu H, Liu J, Toups M, Soos T, Arendt C - BMC Bioinformatics (2016)

Topological localization of drug target genes and signature disease genes. (I) Network-based separation scores of IL17A target genes and signature disease genes of different disease categories. (II) Network connection of IL17A target genes and IBD signature disease genes. Line represents the direct link between the two groups. Green color: IL17A target gene; blue color: IBD signature disease gene; orange color: common gene. Green color with red outline: target genes have direct connection with more than six signature disease genes
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4836068&req=5

Fig8: Topological localization of drug target genes and signature disease genes. (I) Network-based separation scores of IL17A target genes and signature disease genes of different disease categories. (II) Network connection of IL17A target genes and IBD signature disease genes. Line represents the direct link between the two groups. Green color: IL17A target gene; blue color: IBD signature disease gene; orange color: common gene. Green color with red outline: target genes have direct connection with more than six signature disease genes
Mentions: In addition to evaluating the direct gene overlap between drug target and disease signatures, we can also assess the topological distribution of drug target genes and signature disease genes on the interactome. As an example, we calculated the network-based separation score of IL17A target genes and signature disease genes of different disease categories. IL17A plays a pivotal role in psoriasis pathogenesis, and its antagonists show great efficacy in moderate-severe psoriasis patients. Shown in Fig. 8I, the negative separation score indicates that IL17A target genes and psoriasis signature disease genes share overlapping ‘neighborhoods’ and are positioned closely on the interactome. In addition to psoriasis, IL17A target genes also show close relatedness with signature disease genes of other indications, such as IBD, COPD, dermatitis, lupus, and arthritis. To explore the connection between IL17A target genes and IBD signature disease genes, the pair with the lowest separation score, we depict the direct links between the two gene sets on the interactome (Fig. 8II). A total of 148 IL17A target genes and 79 IBD signature disease genes can be mapped to the interactome, including 19 genes in common. Out of the 129 IL17A target-specific genes, 87 have a direct connection with at least one signature disease gene of IBD. Among these, 11 genes (circled in red) have connections with more than six signature disease genes. The close connection of target genes and signature disease genes suggests that the alteration of target genes with drug intervention may potentially have a direct impact on those signature disease genes.Fig. 8

Bottom Line: An in silico approach has been developed to characterize immune cell subsets and diseases based on the gene signatures that most differentiate them from other biological states.This modular 'biomap' reveals the linkages between different diseases and immune subtypes, and provides evidence for the presence of specific immunocyte subsets in mixed tissues.The over-represented genes in disease signatures of interest can be further investigated for their functions in both host defense and disease.

View Article: PubMed Central - PubMed

Affiliation: Bio-Innovation, Sanofi Global Biotherapeutics, 38 Sidney Street, Cambridge, MA, 02139, USA. hong.liu@sanofi.com.

ABSTRACT

Background: The immune system is multifaceted, structured by diverse components that interconnect using multilayered dynamic cellular processes. Genomic technologies provide a means for investigating, at the molecular level, the adaptations of the immune system in host defense and its dysregulation in pathological conditions. A critical aspect of intersecting and investigating complex datasets is determining how to best integrate genomic data from diverse platforms and heterogeneous sample populations to capture immunological signatures in health and disease.

Result: We focus on gene signatures, representing highly enriched genes of immune cell subsets from both diseased and healthy tissues. From these, we construct a series of biomaps that illustrate the molecular linkages between cell subsets from different lineages, the connectivity between different immunological diseases, and the enrichment of cell subset signatures in diseased tissues. Finally, we overlay the downstream genes of drug targets with disease gene signatures to display the potential therapeutic applications for these approaches.

Conclusion: An in silico approach has been developed to characterize immune cell subsets and diseases based on the gene signatures that most differentiate them from other biological states. This modular 'biomap' reveals the linkages between different diseases and immune subtypes, and provides evidence for the presence of specific immunocyte subsets in mixed tissues. The over-represented genes in disease signatures of interest can be further investigated for their functions in both host defense and disease.

No MeSH data available.


Related in: MedlinePlus