gene.iobio: an interactive web tool for versatile, clinically-driven variant interrogation and prioritization

gene.iobio: an interactive web tool for versatile, clinically-driven variant interrogation and prioritization | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article gene.iobio: an interactive web tool for versatile, clinically-driven variant interrogation and prioritization Tonya DiSera, Matt Velinder, Alistair Ward, Yi Qiao, Stephanie Georges, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-402434/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract With increasing utilization of comprehensive genomic data to guide clinical care, anticipated to become the standard of care in many clinical settings, the practice of diagnostic medicine is undergoing a notable shift. However, the move from single-gene or panel-based genetic testing to exome and genome sequencing has not been matched by the development of tools to enable diagnosticians to interpret increasingly complex or uncertain genomic findings. Here, we present gene.iobio, a real-time, intuitive and interactive web application for clinically-driven variant interrogation and prioritization. We show gene.iobio is a novel and effective approach that significantly improves upon and reimagines existing methods. In a radical departure from existing methods that present variants and genomic data in text and table formats, gene.iobio provides an interactive, intuitive and visually-driven analysis environment. We demonstrate that adoption of gene.iobio in clinical and research settings empowers clinical care providers to interact directly with patient genomic data both for establishing clinical diagnoses and informing patient care, using sophisticated genomic analyses that previously were only accessible via complex command line tools. Molecular Genetics Medical Genetics genomic data clinical care gene.iobio Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the manuscript can be downloaded and accessed as a PDF. Additional Declarations No competing interests reported. Supplementary Files SupplementalTable1FeaturesComparison.xlsx FigS1FeaturesComparison.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 02 Jun, 2021 Reviews received at journal 03 May, 2021 Reviewers agreed at journal 22 Apr, 2021 Reviewers invited by journal 21 Apr, 2021 Editor assigned by journal 19 Apr, 2021 Editor invited by journal 13 Apr, 2021 Submission checks completed at journal 12 Apr, 2021 First submitted to journal 07 Apr, 2021 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-402434","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":20850002,"identity":"96e43cce-3719-49fa-a2ed-b8b4180db0b2","order_by":0,"name":"Tonya DiSera","email":"","orcid":"","institution":"University of Utah","correspondingAuthor":false,"prefix":"","firstName":"Tonya","middleName":"","lastName":"DiSera","suffix":""},{"id":20850003,"identity":"1524bb53-2ae9-4866-8e6d-2fcb2bd32969","order_by":1,"name":"Matt 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Utah","correspondingAuthor":false,"prefix":"","firstName":"Ashley","middleName":"","lastName":"Andrews","suffix":""},{"id":20850017,"identity":"39da5e56-6584-4855-bace-632c7025c97d","order_by":15,"name":"Lorenzo Botto","email":"","orcid":"","institution":"University of Utah","correspondingAuthor":false,"prefix":"","firstName":"Lorenzo","middleName":"","lastName":"Botto","suffix":""},{"id":20850018,"identity":"2c4bb7df-21c7-423a-8af6-4b1c0bf412c7","order_by":16,"name":"Gabor Marth","email":"","orcid":"","institution":"University of Utah","correspondingAuthor":false,"prefix":"","firstName":"Gabor","middleName":"","lastName":"Marth","suffix":""}],"badges":[],"createdAt":"2021-04-07 19:44:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-402434/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-402434/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":8012729,"identity":"01562ed4-6c05-4713-892c-29730c4d66e9","added_by":"auto","created_at":"2021-04-14 16:03:15","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":215719,"visible":true,"origin":"","legend":"A representative clinical case as viewed in gene.iobio a) Clinical case information and phenotype\ndescription (not part of gene.iobio). b) Prioritized variants are shown in the left panel and are organized based on their\nreview status, ClinVar pathogenicity, and mode of inheritance. A list of all loaded genes is available in the Genes tab of the\nleft panel. c) Phenotype input components in gene.iobio including: generating a list of genes associated with Coffin Siris\nsyndrome (generated by Phenolyzer), OMIM Gene-Phenotype relationships with inheritance mode and a searchable list\nof PubMed articles associated with the gene. d) Variant details in gene.iobio including variant quality, phenotype\nassociations for the current gene (as generated from the phenotype search component), consequence, gnomAD allele\nfrequency, inheritance and nucleotide conservation. e) Variant review capabilities in gene.iobio including the ability to\nassign a significance (Significant, Unknown significance, Not significant, Poor quality, Not reviewed) as well as enter a\nfree form note.","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-402434/v1/55d273c0fa6a63871365fcee.jpg"},{"id":8013039,"identity":"138146ca-f1d6-4bf8-9fbd-5e9206ef7189","added_by":"auto","created_at":"2021-04-14 16:06:15","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":126783,"visible":true,"origin":"","legend":"An overview of the gene.iobio system and software architecture a) Inputs for gene.iobio include gene\nnames (single or multiple), phenotypes or disorder terms, samples and relatedness between samples, variant files (VCF)\nand sequence alignment files (BAM or CRAM). b) Gene region data (gene genomic coordinates +/- 1000bp) is streamed\nfrom files provided on the user’s local machine or from publicly accessible URLs to a series of backend bioinformatics\nservices. c) gene.iobio coordinates information exchanges between knowledge sources (through APIs where available or\nfrom custom-built iobio backend services) and bioinformatics services to display variant and gene annotations and draw\nvisualizations.","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-402434/v1/440c45009faeae1aae7a4004.jpg"},{"id":8013040,"identity":"0eda780d-21ee-4907-8b6b-3eb2fe68fac5","added_by":"auto","created_at":"2021-04-14 16:06:15","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":135725,"visible":true,"origin":"","legend":"Gene.iobio empowers clinical experts during variant prioritization and is a platform for variant\nreinterpretation a) In a representative clinical case of a male between 30 and 40 years old with adult onset\nleukodystrophy, gene.iobio provides comprehensive variant and clinical information that supports the candidate ATP6AP2\nvariant. b) In the same clinical case, gene.iobio provides comprehensive variant and clinical information to refute the\ncandidate BRWD3 variant. c) Reanalysis of a previously undiagnosed case in gene.iobio reveals an updated pathogenic\nClinVar assertion for a candidate variant in the SON gene.","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-402434/v1/07f3274a27e921994589b65a.jpg"},{"id":8012727,"identity":"efeed3e8-b13f-4688-b6e7-47c7175ac85b","added_by":"auto","created_at":"2021-04-14 16:03:15","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":179008,"visible":true,"origin":"","legend":"Gene.iobio helps adjudicate de novo variants, identify Mendelian violations and provides on-demand\nvariant calling a) Adjudication of a false negative de novo variant in gene.iobio where reasonable allele balance, despite\nlow coverage, suggest the variant could be real. b) Adjudication of a false positive de novo variant in gene.iobio where\npoor allele balance suggests the variant is likely not real. c) Adjudication of a false positive de novo variant in gene.iobio\nwhere variant evidence is observed in both parents, suggesting the variant could be inherited and not a real de novo. d) A\nMendelian violation viewed in gene.iobio where a sibling has a heterozygous genotype, despite both parents being\nhomozygous alternate, a clear Mendelian violation. e) On-demand variant calling in gene.iobio using Freebayes where a\nprevious variant calling method failed to call any variants in the DGCR2 gene, but Freebayes variant calling in gene.iobio\nidentifies numerous variants within the gene.","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-402434/v1/2057c47d9988fce416c97800.jpg"},{"id":13621892,"identity":"f829249b-9edb-430c-8965-ac295f84bd54","added_by":"auto","created_at":"2021-09-17 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limitations, full-text HTML conversion of this manuscript could not be completed. 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We demonstrate that adoption of gene.iobio in clinical and research settings empowers clinical care providers to interact directly with patient genomic data both for establishing clinical diagnoses and informing patient care, using sophisticated genomic analyses that previously were only accessible via complex command line tools.","manuscriptTitle":"gene.iobio: an interactive web tool for versatile, clinically-driven variant interrogation and prioritization","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-04-14 16:03:13","doi":"10.21203/rs.3.rs-402434/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2021-06-02T09:08:50+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2021-05-04T03:37:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"b79905a5-044b-49c0-9451-7175e81ddc84","date":"2021-04-22T06:24:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2021-04-21T07:48:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2021-04-19T22:32:22+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2021-04-13T17:49:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2021-04-12T06:20:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2021-04-07T19:36:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"de8bda80-4bb0-4a4b-8a08-7f80c800e63a","owner":[],"postedDate":"April 14th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":3641912,"name":"Molecular Genetics"},{"id":3641913,"name":"Medical Genetics"}],"tags":[],"updatedAt":"2021-09-03T12:59:06+00:00","versionOfRecord":[],"versionCreatedAt":"2021-04-14 16:03:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-402434","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-402434","identity":"rs-402434","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}