One-Sided Matching Portal (OSMP): A Tool to Facilitate Rare Disease Patient Matchmaking

IF 3.7 2区医学 Q2 GENETICS & HEREDITY

Human Mutation Pub Date : 2025-10-09 DOI:10.1155/humu/5941599

Matthew Osmond, E. Magda Price, Orion J. Buske, Mackenzie Frew, Madeline Couse, Taila Hartley, Conor Klamann, Hannah G. B. H. Le, Jenny Xu, Delvin So, Anjali Jain, Kevin Lu, Kevin Mo, Hannah Wyllie, Erika Wall, Hannah G. Driver, Warren A. Cheung, Ana S. A. Cohen, Emily G. Farrow, Isabelle Thiffault, Care4Rare Canada Consortium, Andrei L. Turinsky, Tomi Pastinen, Michael Brudno, Kym M. Boycott

{"title":"One-Sided Matching Portal (OSMP): A Tool to Facilitate Rare Disease Patient Matchmaking","authors":"Matthew Osmond, E. Magda Price, Orion J. Buske, Mackenzie Frew, Madeline Couse, Taila Hartley, Conor Klamann, Hannah G. B. H. Le, Jenny Xu, Delvin So, Anjali Jain, Kevin Lu, Kevin Mo, Hannah Wyllie, Erika Wall, Hannah G. Driver, Warren A. Cheung, Ana S. A. Cohen, Emily G. Farrow, Isabelle Thiffault, Care4Rare Canada Consortium, Andrei L. Turinsky, Tomi Pastinen, Michael Brudno, Kym M. Boycott","doi":"10.1155/humu/5941599","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Background</h3>\n \n <p>Genomic matchmaking—the process of identifying individuals with overlapping phenotypes and rare variants in the same gene—is an important tool facilitating gene discoveries for unsolved rare genetic disease (RGD) patients. Current approaches are two-sided, meaning both patients being matched must have the same candidate gene flagged. This limits the number of RGD patients eligible for matchmaking. One-sided matchmaking, in which a gene of interest is queried in the genome-wide sequencing data of RGD patients, would make matchmaking possible for previously undiscoverable individuals. However, platforms and workflows for this approach have not been well established.</p>\n </section>\n \n <section>\n \n <h3> Result</h3>\n \n <p>We released a beta version of the One-Sided Matching Portal (OSMP), a platform capable of performing one-sided matchmaking queries across thousands of participants stored in genomic databases. The OSMP returns variant-level and participant-level information on each variant occurrence (VO) identified in a queried gene. A workflow for one-sided matchmaking was developed so that researchers could prioritize the many VOs returned from a given query. This workflow was tested through pilot studies where two sets of genes were queried in over 2500 individuals: 130 genes that were newly associated with disease in OMIM and 178 novel candidate genes that were not associated with a disease-gene association in OMIM. These pilots returned a large number of initial VOs (12,872 and 20,308, respectively); however, the workflow filtered out over 99.8% of these VOs prior to review by a participant’s clinician. Filters on participant-level information, including variant zygosity, participant phenotype, and whether a variant was also present in unaffected participants, were effective at reducing the number of false positive matches.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>As demonstrated through the two pilot studies, one-sided matchmaking queries can be efficiently performed using the OSMP. The availability of variant-level and participant-level data is key to ensuring this approach is practical for researchers.</p>\n </section>\n </div>","PeriodicalId":13061,"journal":{"name":"Human Mutation","volume":"2025 1","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/humu/5941599","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Mutation","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/humu/5941599","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Genomic matchmaking—the process of identifying individuals with overlapping phenotypes and rare variants in the same gene—is an important tool facilitating gene discoveries for unsolved rare genetic disease (RGD) patients. Current approaches are two-sided, meaning both patients being matched must have the same candidate gene flagged. This limits the number of RGD patients eligible for matchmaking. One-sided matchmaking, in which a gene of interest is queried in the genome-wide sequencing data of RGD patients, would make matchmaking possible for previously undiscoverable individuals. However, platforms and workflows for this approach have not been well established.

Result

We released a beta version of the One-Sided Matching Portal (OSMP), a platform capable of performing one-sided matchmaking queries across thousands of participants stored in genomic databases. The OSMP returns variant-level and participant-level information on each variant occurrence (VO) identified in a queried gene. A workflow for one-sided matchmaking was developed so that researchers could prioritize the many VOs returned from a given query. This workflow was tested through pilot studies where two sets of genes were queried in over 2500 individuals: 130 genes that were newly associated with disease in OMIM and 178 novel candidate genes that were not associated with a disease-gene association in OMIM. These pilots returned a large number of initial VOs (12,872 and 20,308, respectively); however, the workflow filtered out over 99.8% of these VOs prior to review by a participant’s clinician. Filters on participant-level information, including variant zygosity, participant phenotype, and whether a variant was also present in unaffected participants, were effective at reducing the number of false positive matches.

Conclusion

As demonstrated through the two pilot studies, one-sided matchmaking queries can be efficiently performed using the OSMP. The availability of variant-level and participant-level data is key to ensuring this approach is practical for researchers.

Abstract Image

查看原文本刊更多论文

单方面匹配门户（OSMP）：一个工具，以促进罕见疾病患者配对

基因组配对是鉴定具有重叠表型和相同基因罕见变异的个体的过程，是促进未解决的罕见遗传病（RGD）患者基因发现的重要工具。目前的方法是双向的，这意味着两个匹配的患者必须有相同的候选基因标记。这限制了符合配对条件的RGD患者的数量。单侧配对，在RGD患者的全基因组测序数据中查询感兴趣的基因，将使以前未发现的个体配对成为可能。然而，这种方法的平台和工作流还没有很好地建立起来。我们发布了单侧配对门户（OSMP）的测试版，该平台能够对存储在基因组数据库中的数千名参与者进行单侧配对查询。OSMP返回在查询的基因中确定的每个变异发生（VO）的变异水平和参与者水平信息。开发了一个单侧匹配的工作流程，以便研究人员可以优先考虑从给定查询返回的许多VOs。该工作流程通过试点研究进行了测试，其中在2500多人中查询了两组基因：130个与OMIM疾病新相关的基因和178个与OMIM疾病基因关联无关的新候选基因。这些飞行员返回了大量初始VOs（分别为12,872和20,308）；然而，在参与者的临床医生审查之前，工作流程过滤掉了超过99.8%的这些VOs。筛选参与者水平的信息，包括变异合子，参与者表型，以及是否在未受影响的参与者中也存在变异，可以有效地减少假阳性匹配的数量。通过两个试点研究表明，使用OSMP可以有效地执行单侧配对查询。变量水平和参与者水平数据的可用性是确保该方法对研究人员实用的关键。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Human Mutation 医学-遗传学

CiteScore

8.40

自引率

5.10%

发文量

190

审稿时长

2 months

期刊介绍： Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.