{"doi":"10.1016/j.cels.2017.06.016","title":"Comprehensive Analysis of Tissue-wide Gene Expression and Phenotype Data Reveals Tissues Affected in Rare Genetic Disorders","abstract":"Linking putatively pathogenic variants to the tissues they affect is necessary for determining the correct diagnostic workup and therapeutic regime in undiagnosed patients. Here, we explored how gene expression across healthy tissues can be used to infer this link. We integrated 6,665 tissue-wide transcriptomes with genetic disorder knowledge bases covering 3,397 diseases. Receiver-operating characteristics (ROC) analysis using expression levels in each tissue and across tissues indicated significant but modest associations between elevated expression and phenotype for most tissues (maximum area under ROC curve = 0.69). At extreme elevation, associations were marked. Upregulation of disease genes in affected tissues was pronounced for genes associated with autosomal dominant over recessive disorders. Pathways enriched for genes expressed and associated with phenotypes highlighted tissue functionality, including lipid metabolism in spleen and DNA repair in adipose tissue. These results suggest features useful for evaluating the likelihood of particular tissue manifestations in genetic disorders. The web address of an interactive platform integrating these data is provided.","journal":"Cell Systems","year":2017,"id":12044,"datarank":1.3665471400907114,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.8962230077013389,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.8962230077013389,"corpus_percentile":61.02522375915378,"corpus_rank":480,"citation_count":22,"citer_count":23,"citers_with_citation_signal":18,"citers_with_endowment":18,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8472,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2017-08-01","fair_score":35.9167,"fair_percentile":17.788038698328936,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":96017,"name":"Bryce K. Allen","orcid":"0000-0002-0804-8127","position":1,"is_corresponding":false},{"id":3527,"name":"Isaac S. Kohane","orcid":"0000-0003-2192-5160","position":2,"is_corresponding":false},{"id":96018,"name":"Sek Won Kong","orcid":"0000-0003-4877-7567","position":3,"is_corresponding":false},{"id":96016,"name":"Ariel Feiglin","orcid":"0000-0003-2862-7668","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":"28822752","pmcid":"PMC5928498","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":69.0,"fair_a":53.0,"fair_i":5.0,"fair_r":16.6667,"fair_zscore":-0.8408,"fair_rationale":{"fair_score":35.92,"has_llm":true,"dimensions":{"F":{"name":"Findable","score":69.0,"criteria":[{"key":"f_has_doi","label":"Has a persistent DOI","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"DOI present","rationale":null},{"key":"f_repository_presence","label":"Indexed in repositories / literature DBs","kind":"deterministic","weight":1.0,"fraction":1.0,"signal":"datacite=0, pmcid=True, pmid=True","rationale":null},{"key":"f_persistent_ids","label":"Resolvable scholarly identifiers (OpenAlex)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no OpenAlex id","rationale":null},{"key":"f_metadata_richness","label":"Rich, machine-readable metadata","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"The paper does not mention any machine-readable metadata or structured descriptions of the data."}]},"A":{"name":"Accessible","score":53.0,"criteria":[{"key":"a_open_access","label":"Open Access / files deposited","kind":"deterministic","weight":1.5,"fraction":1.0,"signal":"Open Access","rationale":null},{"key":"a_retrievable","label":"Free full text retrievable","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"0 OA location(s)","rationale":null},{"key":"a_access_protocol","label":"Clear data/code access protocol","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"Only a web address for an interactive platform is provided, without details on data download or access protocols."}]},"I":{"name":"Interoperable","score":5.0,"criteria":[{"key":"i_linked_data","label":"Linked datasets / DataCite relations","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"linked_datasets=0, datacite=0","rationale":null},{"key":"i_standard_ids","label":"References data via standard accessions","kind":"deterministic","weight":1.0,"fraction":0.0,"signal":"accessions=0, trials=0","rationale":null},{"key":"i_standards","label":"Standard formats, vocabularies & identifiers","kind":"llm","weight":1.0,"fraction":0.25,"signal":null,"rationale":"No mention of standard formats, controlled vocabularies, or persistent identifiers like DOIs for datasets."}]},"R":{"name":"Reusable","score":16.67,"criteria":[{"key":"r_license","label":"Clear, open reuse license","kind":"deterministic","weight":1.5,"fraction":0.0,"signal":"no license","rationale":null},{"key":"r_downloads","label":"Demonstrated reuse (downloads)","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"downloads=0","rationale":null},{"key":"r_version","label":"Versioned / maintained","kind":"deterministic","weight":0.5,"fraction":0.0,"signal":"no version chain","rationale":null},{"key":"r_dataset","label":"Classified as a data resource","kind":"deterministic","weight":0.5,"fraction":1.0,"signal":"is_dataset","rationale":null},{"key":"r_reusability","label":"Data-availability statement, license & reproducibility","kind":"llm","weight":2.0,"fraction":0.167,"signal":null,"rationale":"No data-availability statement, license, or reproducibility information is provided beyond a vague platform reference."}]}},"suggestions":["Deposit raw and processed data in a FAIR-aligned repository with rich metadata, licenses, and persistent identifiers.","Provide a formal data-availability statement specifying access conditions and licenses for all datasets.","Use standard gene and phenotype ontologies (e.g., Ensembl IDs, HPO) and document file formats (e.g., CSV, TSV).","Include a reproducibility section describing software versions, parameters, and analysis pipelines."],"model":"deepseek/deepseek-v4-flash","agent_version":"fair_agent_v2","fulltext_source":"abstract_only"},"fair_model":"deepseek/deepseek-v4-flash","fair_agent_version":"fair_agent_v2","fair_fulltext_source":"abstract_only","fair_has_llm":true,"fair_computed_at":"2026-06-18T00:47:17.183663Z","clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}