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useful_tools_for_functional_and_pathway_analysis [2018/06/25 12:26] – external edit 127.0.0.1useful_tools_for_functional_and_pathway_analysis [2019/10/31 16:40] admin
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-=====   =====+===== Useful tools for functional and pathway analysis ===== 
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 +  * [[http://www.humanmine.org/%20|Humanmine ]] : given a list of genes as input (Entrez/Ensembl/Symbol or a mix), it returns interaction networks, pathways, Gene Ontology categories, relevant literature, protein domains, chromosome distributions and much more on a single page. There are also nice summaries that pop-up by hovering the mouse over a gene name.
  
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-  * [[http://www.humanmine.org/%20|Humanmine ]] : given a list of genes as input (Entrez/Ensembl/Symbol or a mix), it returns interaction networks, pathways, Gene Ontology categories, relevant literature, protein domains, chromosome distributions and much more on a single page. There are also nice summaries that pop-up by hovering the mouse over a gene name.\\ \\ 
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   * [[http://www.genemania.org/|GeneMANIA]] performs functional analysis using protein and genetic interactions, pathways, co-expression, co-localization and protein domain similarity.   * [[http://www.genemania.org/|GeneMANIA]] performs functional analysis using protein and genetic interactions, pathways, co-expression, co-localization and protein domain similarity.
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   * [[http://www.drugbank.ca/downloads#external-links|DrugBank]] has [[http://www.drugbank.ca/stats|many ]]drug-target interactions.   * [[http://www.drugbank.ca/downloads#external-links|DrugBank]] has [[http://www.drugbank.ca/stats|many ]]drug-target interactions.
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   * Also see [[http://stitch.embl.de/|STICH ]]for predicted and known chemical-protein interactions.   * Also see [[http://stitch.embl.de/|STICH ]]for predicted and known chemical-protein interactions.
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   * [[http://www.broadinstitute.org/gsea/msigdb/index.jsp%20|MSIGDB ]]has around 10,000 sets (collections) of interesting genes, including curated sets from publications (e.g. genes affected by specific genetic and chemical perturbations), canonical pathways, GO, microRNA and transcription factor (TF) targets, as well as Hallmarks of particular processes, oncogenic signatures and more. We have some custom made scripts for mining these sets. The BROAD institute has also their own software with sleek GUIs (GSEA).   * [[http://www.broadinstitute.org/gsea/msigdb/index.jsp%20|MSIGDB ]]has around 10,000 sets (collections) of interesting genes, including curated sets from publications (e.g. genes affected by specific genetic and chemical perturbations), canonical pathways, GO, microRNA and transcription factor (TF) targets, as well as Hallmarks of particular processes, oncogenic signatures and more. We have some custom made scripts for mining these sets. The BROAD institute has also their own software with sleek GUIs (GSEA).
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   * In addition to TFT collection from MSigDB, other resources for identifying transcription factor targets include: [[http://www.biobase-international.com/gene-regulation|TRANSFAC]], [[https://en.wikipedia.org/wiki/Open_Regulatory_Annotation_Database|ORegAnno]] and [[https://github.com/slowkow/tftargets|tftargets]]. Alternatives computational tools, such as [[http://meme-suite.org/|MEME]], [[http://pazar.info/|PAZAR]], and [[http://itfp.biosino.org/itfp/|ITFP]], should be used with care because their predictions are not as reliable as targets validated by real experiments.   * In addition to TFT collection from MSigDB, other resources for identifying transcription factor targets include: [[http://www.biobase-international.com/gene-regulation|TRANSFAC]], [[https://en.wikipedia.org/wiki/Open_Regulatory_Annotation_Database|ORegAnno]] and [[https://github.com/slowkow/tftargets|tftargets]]. Alternatives computational tools, such as [[http://meme-suite.org/|MEME]], [[http://pazar.info/|PAZAR]], and [[http://itfp.biosino.org/itfp/|ITFP]], should be used with care because their predictions are not as reliable as targets validated by real experiments.
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-  +  * [[https://cran.r-project.org/web/packages/gProfileR/index.html|gProfileR]] does Pathway,GO,TF,microRNA,OMIM, and Phenotype over-representation analysis, with quite up to date annotations. 
-  * [[https://cran.r-project.org/web/packages/gProfileR/index.html|gProfileR]] does Pathway,GO,TF,microRNA,OMIM, and Phenotype over-representation analysis, with quite up to date annotations.\\ \\ +
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   * [[http://tcng.hgc.jp/index.html?t=network&id=27|TCNG]], a cancer gene network of potential interest.   * [[http://tcng.hgc.jp/index.html?t=network&id=27|TCNG]], a cancer gene network of potential interest.
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   * [[http://www.stemformatics.org/contents/index#tutorial=guest|Stemfomatics]], visualizes genes in exemplar stem cell datasets.   * [[http://www.stemformatics.org/contents/index#tutorial=guest|Stemfomatics]], visualizes genes in exemplar stem cell datasets.
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   * [[http://www.innatedb.com|InnateDB]]contains many (over 100,000) experimentally validated interactions (with some bias towards immunity related genes) as well as pathway, gene ontology and visualization tools.   * [[http://www.innatedb.com|InnateDB]]contains many (over 100,000) experimentally validated interactions (with some bias towards immunity related genes) as well as pathway, gene ontology and visualization tools.
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   * [[https://peerj.com/articles/229/|SIGORA]] an alternative pathway analysis tool that focuses on features that are unique to each pathway.   * [[https://peerj.com/articles/229/|SIGORA]] an alternative pathway analysis tool that focuses on features that are unique to each pathway.
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-  +  * Additional resources worth exploring: \\ [[http://data-analysis.charite.de/care/|http://data-analysis.charite.de/care/]] \\  [[http://geneanswers.nubic.northwestern.edu/|http://geneanswers.nubic.northwestern.edu/]] 
-  * Additional resources worth exploring:\\ http://data-analysis.charite.de/care/\\ http://geneanswers.nubic.northwestern.edu/ +
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   * [[https://www.proteinspire.org/MOPED/mopedviews/proteinExpressionDatabase.jsf|MOPED]]   * [[https://www.proteinspire.org/MOPED/mopedviews/proteinExpressionDatabase.jsf|MOPED]]
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   * BioConductor package [[https://www.bioconductor.org/packages/3.3/bioc/manuals/mgsa/man/mgsa.pdf|mgsa]] ; [[http://nar.oxfordjournals.org/content/early/2010/02/19/nar.gkq045|Paper]] (using Bayesian networks and MCMC instead of over-representation analysis for determining relevant Gene Ontology terms). Might be more useful as an original conceptual reference point than a revolutionary practical tool.   * BioConductor package [[https://www.bioconductor.org/packages/3.3/bioc/manuals/mgsa/man/mgsa.pdf|mgsa]] ; [[http://nar.oxfordjournals.org/content/early/2010/02/19/nar.gkq045|Paper]] (using Bayesian networks and MCMC instead of over-representation analysis for determining relevant Gene Ontology terms). Might be more useful as an original conceptual reference point than a revolutionary practical tool.
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-  * Cancer and Tissue type specific PPIs and miRNA-targets: [[http://bis.zju.edu.cn/CancerNet/download.jsp|CancerNet ]]([[http://www.nature.com/oncsis/journal/v4/n12/full/oncsis201540a.html|Paper]]) //"Experimentally detected PPIs were assembled from five major PPI databases and miRNA–target interactions were considered as the combination of the predicted targets from six algorithms and two experimentally validated data sets, amounting to 185 589 PPIs and 3 249 385 miRNA–target interactions, respectively. Synergistic miRNA pairs were predicted according to the functions of target genes as well as their proximity in the PPI network."// E.g. for HCC, there are ~130,000 protein-protein interactions listed here. +  * Cancer and Tissue type specific PPIs and miRNA-targets: [[http://bis.zju.edu.cn/CancerNet/download.jsp|CancerNet ]]([[http://www.nature.com/oncsis/journal/v4/n12/full/oncsis201540a.html|Paper]]) //"Experimentally detected PPIs were assembled from five major PPI databases and miRNA–target interactions were considered as the combination of the predicted targets from six algorithms and two experimentally validated data sets, amounting to 185 589 PPIs and 3 249 385 miRNA–target interactions, respectively. Synergistic miRNA pairs were predicted according to the functions of target genes as well as their proximity in the PPI network."//  E.g. for HCC, there are ~130,000 protein-protein interactions listed here. 
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   * [[http://seek.princeton.edu/viewer33.jsp?sessionID=1452571188159&sort_sample_by_expr=true|SEEK]]. User's query: A list of genes. Returns a ranking of datasets in which the input genes are co-expressed, also, the list of other co-expressed genes. User can prioritizes ~5000 expression datasets based on tissue or disease.   * [[http://seek.princeton.edu/viewer33.jsp?sessionID=1452571188159&sort_sample_by_expr=true|SEEK]]. User's query: A list of genes. Returns a ranking of datasets in which the input genes are co-expressed, also, the list of other co-expressed genes. User can prioritizes ~5000 expression datasets based on tissue or disease.
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   * An old (2010) survey of approaches for gene list [[http://jura.wi.mit.edu/bio/education/hot_topics/enrichment/Gene_list_enrichment_Mar10.pdf|enrichment]] analysis.   * An old (2010) survey of approaches for gene list [[http://jura.wi.mit.edu/bio/education/hot_topics/enrichment/Gene_list_enrichment_Mar10.pdf|enrichment]] analysis.
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-  * Look up genes, cancers, translocations, case studies, find high quality papers: http://atlasgeneticsoncology.org +  * Look up genes, cancers, translocations, case studies, find high quality papers: [[http://atlasgeneticsoncology.org|http://atlasgeneticsoncology.org]] 
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   * [[http://www.genomicus.biologie.ens.fr/genomicus-83.01/cgi-bin/search.pl|Genomicus]]: Facilitates navigation in genomes in several dimensions: linearly along chromosome axes, transversaly across different species, and chronologicaly along evolutionary time.   * [[http://www.genomicus.biologie.ens.fr/genomicus-83.01/cgi-bin/search.pl|Genomicus]]: Facilitates navigation in genomes in several dimensions: linearly along chromosome axes, transversaly across different species, and chronologicaly along evolutionary time.
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   * [[https://www.bioconductor.org/packages/release/bioc/vignettes/FGNet/inst/doc/FGNet.html|FGNet]], Performs **F**unctional **G**ene **Net**work analysis. Uses DAVID, Gene-Term Linker, TopGo, and GAGE (GSEA) directly from R, also with a graphical user interphase.   * [[https://www.bioconductor.org/packages/release/bioc/vignettes/FGNet/inst/doc/FGNet.html|FGNet]], Performs **F**unctional **G**ene **Net**work analysis. Uses DAVID, Gene-Term Linker, TopGo, and GAGE (GSEA) directly from R, also with a graphical user interphase.
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   * [[https://www.bioconductor.org/packages/release/bioc/vignettes/pwOmics/inst/doc/pwOmics.pdf|pwOmics]], an R package that integrates proteomics and transcriptomics data, and performs pathway, protein-protein interaction, and transcription factor analyses.   * [[https://www.bioconductor.org/packages/release/bioc/vignettes/pwOmics/inst/doc/pwOmics.pdf|pwOmics]], an R package that integrates proteomics and transcriptomics data, and performs pathway, protein-protein interaction, and transcription factor analyses.
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   * Free alternatives to Ingenuity Pathway Analysis ([[https://www.biostars.org/p/6203/|IPA]]).   * Free alternatives to Ingenuity Pathway Analysis ([[https://www.biostars.org/p/6203/|IPA]]).
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   * See [[https://www.biostars.org/p/6203/|this]] Biostar trend for updates on recent tools such as [[http://www.pathwaycommons.org/pc/|Pathwaycommons]], a kind of integrated approach including [[http://www.reactome.org/|Reactome]], and [[https://pathview.uncc.edu/|Pathview Web server]] .   * See [[https://www.biostars.org/p/6203/|this]] Biostar trend for updates on recent tools such as [[http://www.pathwaycommons.org/pc/|Pathwaycommons]], a kind of integrated approach including [[http://www.reactome.org/|Reactome]], and [[https://pathview.uncc.edu/|Pathview Web server]] .
-\\ +  * The Human [[https://www.proteinatlas.org/|Protein Atlas]] is useful to get information on the expression of a particular protein at the cellular, normal tissue, and tumor levels. 
 +  * There are some [[https://www.biostars.org/p/274514/|R tools]] for pathway analysis including [[https://yulab-smu.github.io/clusterProfiler-book/|ClusterProfiler]]. 
 +  * Mouse Genome Informatics ([[http://www.informatics.jax.org/|MGI]]) has a nice hierarchal Gene Ontology [[http://www.informatics.jax.org/vocab/gene_ontology|Browser]] similar to Reactome. 
 +  * Isha's list of [[https://docs.google.com/presentation/d/1c4HAcImyyU1as5qEwzmH8QIAxD25N4Z5__sUZE3n6kk/edit#slide=id.g6f90f06c9f_0_0|functional enrichment]] analysis tools in R. 
 ==== Reference: ==== ==== Reference: ====
-Khatri, Purvesh, Marina Sirota, and Atul J. Butte. "Ten years of pathway analysis: current approaches and outstanding challenges." //PLoS [[http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002375|Comput]] Biol// 8.2 (2012): e1002375. A good survey. Criticized DE and overrepresentation analyses.+ 
 +Khatri, Purvesh, Marina Sirota, and Atul J. Butte. "Ten years of pathway analysis: current approaches and outstanding challenges." //PLoS [[http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002375|Comput]] Biol//8.2 (2012): e1002375. A good survey. Criticized DE and overrepresentation analyses. 
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