Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling
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{"title"=>"Pathway network analyses for autism reveal multisystem involvement, major overlaps with other diseases and convergence upon MAPK and calcium signaling", "type"=>"journal", "authors"=>[{"first_name"=>"Ya", "last_name"=>"Wen", "scopus_author_id"=>"57188839832"}, {"first_name"=>"Mohamad J.", "last_name"=>"Alshikho", "scopus_author_id"=>"57188837843"}, {"first_name"=>"Martha R.", "last_name"=>"Herbert", "scopus_author_id"=>"7103313028"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84963718872", "sgr"=>"84963718872", "pui"=>"609703281", "pmid"=>"27055244", "doi"=>"10.1371/journal.pone.0153329"}, "id"=>"3e203ac4-6551-32af-ae56-1ae764e5864c", "abstract"=>"We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging-they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)-and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process \"calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK\" is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG's category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions and heart diseases. ASDs may thus arise, or emerge, from underlying vulnerabilities related to pleiotropic genes associated with pervasively important molecular mechanisms, vulnerability to environmental input and multiple systemic co-morbidities.", "link"=>"http://www.mendeley.com/research/pathway-network-analyses-autism-reveal-multisystem-involvement-major-overlaps-other-diseases-converg", "reader_count"=>61, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Researcher"=>14, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>9, "Student > Master"=>5, "Other"=>5, "Student > Bachelor"=>11, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Researcher"=>14, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>9, "Student > Master"=>5, "Other"=>5, "Student > Bachelor"=>11, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>14, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>10, "Neuroscience"=>8, "Business, Management and Accounting"=>1, "Psychology"=>2, "Social Sciences"=>3}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Neuroscience"=>{"Neuroscience"=>8}, "Social Sciences"=>{"Social Sciences"=>3}, "Psychology"=>{"Psychology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>14}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Hungary"=>1, "United States"=>1, "Brazil"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4927393", "https://ndownloader.figshare.com/files/4927396", "https://ndownloader.figshare.com/files/4927399"], "description"=>"<div><p>We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging—they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)—and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process “calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK” is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG’s category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions and heart diseases. ASDs may thus arise, or emerge, from underlying vulnerabilities related to pleiotropic genes associated with pervasively important molecular mechanisms, vulnerability to environmental input and multiple systemic co-morbidities.</p></div>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164134, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0153329.s001", "https://dx.doi.org/10.1371/journal.pone.0153329.s002", "https://dx.doi.org/10.1371/journal.pone.0153329.s003"], "stats"=>{"downloads"=>6, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pathway_Network_Analyses_for_Autism_Reveal_Multisystem_Involvement_Major_Overlaps_with_Other_Diseases_and_Convergence_upon_MAPK_and_Calcium_Signaling/3164134", "title"=>"Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-04-07 05:14:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927483"], "description"=>"<p>Pathway groupings and pathway-pathway interactions.</p>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164200, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153329.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pathway_groupings_and_pathway_pathway_interactions_/3164200", "title"=>"Pathway groupings and pathway-pathway interactions.", "pos_in_sequence"=>6, "defined_type"=>3, "published_date"=>"2016-04-07 05:14:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927561"], "description"=>"<p>ASD genes in the pathway neuroactive ligand-receptor interaction.</p>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164266, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153329.t004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/ASD_genes_in_the_pathway_neuroactive_ligand_receptor_interaction_/3164266", "title"=>"ASD genes in the pathway neuroactive ligand-receptor interaction.", "pos_in_sequence"=>9, "defined_type"=>3, "published_date"=>"2016-04-07 05:14:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927405"], "description"=>"<p>Pathways were grouped into subsets of two classes. Pathways in the Disease class are surrounded by a black border; the remainder of the pie chart sections are in the Functional class. Labels indicate pathway groupings (number of pathways in grouping/percentage of total number of pathways).</p>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164140, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153329.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pathway_groupings_/3164140", "title"=>"Pathway groupings.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927453"], "description"=>"<p>a. Overlapping genes in calcium and MAPK signaling pathways. b. The voltage-gated calcium channel mediates the influx of Ca<sup>2+</sup>, which modulates PKC and Ras. Growth factors bind to the extracellular domain of receptor tyrosine kinases (RTKs), and signal molecules Grb2 (growth factor receptor-bound protein 2) and Sos (son of sevenless) are consequently recruited to the internal docking site, resulting in Ras activation. Ras triggers a phosphorylation cascade including Raf and MEK. This leads to ERK activation and translocation to the nucleus, where ERK then activates transcription factors that mediate gene expression. The ASD genes are listed in light blue frames close to the corresponding gene products that are shown in orange.</p>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164173, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153329.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Integrated_MAPK_and_calcium_signaling_in_ASDs_/3164173", "title"=>"Integrated MAPK and calcium signaling in ASDs.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927534"], "description"=>"<p>Involvement of ASD genes in the ASD pathway network.</p>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164242, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153329.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Involvement_of_ASD_genes_in_the_ASD_pathway_network_/3164242", "title"=>"Involvement of ASD genes in the ASD pathway network.", "pos_in_sequence"=>8, "defined_type"=>3, "published_date"=>"2016-04-07 05:14:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/4927465"], "description"=>"<p>The flow chart in <b>a,</b> summarizes the analyses and related results. The conclusions are visualized into a cellular model in <b>b.</b> The relationship between genes, gene products, environmental information processing and phenotypes is schematized in <b>c</b>.</p>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164182, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153329.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_systematic_biological_framework_/3164182", "title"=>"A systematic biological framework.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-07 05:14:01"}
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  • {"files"=>["https://ndownloader.figshare.com/files/4927504"], "description"=>"<p>Enrichment analyses for gene ontologies.</p>", "links"=>[], "tags"=>["autism spectrum disorders", "ASD", "Autism Reveal Multisystem Involvement", "Simons Foundation Autism Research Initiative", "gene", "Pathway Network Analyses", "KEGG", "enrichment analysis", "pathway network components", "SFARI", "MAPK"], "article_id"=>3164221, "categories"=>["Biochemistry", "Medicine", "Microbiology", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Biological Sciences not elsewhere classified", "Cancer", "Mental Health", "Infectious Diseases", "Computational Biology"], "users"=>["Ya Wen", "Mohamad J. Alshikho", "Martha R. Herbert"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153329.t002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Enrichment_analyses_for_gene_ontologies_/3164221", "title"=>"Enrichment analyses for gene ontologies.", "pos_in_sequence"=>7, "defined_type"=>3, "published_date"=>"2016-04-07 05:14:01"}

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{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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