{"id":971,"date":"2022-10-28T12:16:15","date_gmt":"2022-10-28T04:16:15","guid":{"rendered":"https:\/\/spinebigdata.com\/?p=971"},"modified":"2024-03-21T16:21:57","modified_gmt":"2024-03-21T08:21:57","slug":"%e8%af%be%e9%a2%98%e7%bb%84%e4%ba%8ethe-american-journal-of-human-genetics%e5%8f%91%e8%a1%a8%e7%a0%94%e7%a9%b6%e6%96%87%e7%ab%a0","status":"publish","type":"post","link":"https:\/\/spinebigdata.com\/?p=971","title":{"rendered":"\u8bfe\u9898\u7ec4\u4e8eThe American Journal of Human Genetics\u53d1\u8868\u7814\u7a76\u8bba\u6587"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"971\" class=\"elementor elementor-971\" data-elementor-post-type=\"post\">\n\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-2303839d elementor-section-height-min-height elementor-section-boxed elementor-section-height-default elementor-section-items-middle\" data-id=\"2303839d\" data-element_type=\"section\" data-e-type=\"section\" data-settings=\"{&quot;background_background&quot;:&quot;gradient&quot;,&quot;shape_divider_bottom&quot;:&quot;waves&quot;}\">\n\t\t\t\t\t\t\t<div class=\"elementor-background-overlay\"><\/div>\n\t\t\t\t\t\t<div class=\"elementor-shape elementor-shape-bottom\" aria-hidden=\"true\" data-negative=\"false\">\n\t\t\t<svg xmlns=\"http:\/\/www.w3.org\/2000\/svg\" viewBox=\"0 0 1000 100\" preserveAspectRatio=\"none\">\n\t<path class=\"elementor-shape-fill\" d=\"M421.9,6.5c22.6-2.5,51.5,0.4,75.5,5.3c23.6,4.9,70.9,23.5,100.5,35.7c75.8,32.2,133.7,44.5,192.6,49.7\n\tc23.6,2.1,48.7,3.5,103.4-2.5c54.7-6,106.2-25.6,106.2-25.6V0H0v30.3c0,0,72,32.6,158.4,30.5c39.2-0.7,92.8-6.7,134-22.4\n\tc21.2-8.1,52.2-18.2,79.7-24.2C399.3,7.9,411.6,7.5,421.9,6.5z\"\/>\n<\/svg>\t\t<\/div>\n\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-d30ad9e\" data-id=\"d30ad9e\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-c8a5788 elementor-widget elementor-widget-theme-post-title elementor-page-title elementor-widget-heading\" data-id=\"c8a5788\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"theme-post-title.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h1 class=\"elementor-heading-title elementor-size-default\">\u8bfe\u9898\u7ec4\u4e8eThe American Journal of Human Genetics\u53d1\u8868\u7814\u7a76\u8bba\u6587<\/h1>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-2a186618 elementor-align-center elementor-widget elementor-widget-post-info\" data-id=\"2a186618\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"post-info.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<ul class=\"elementor-inline-items elementor-icon-list-items elementor-post-info\">\n\t\t\t\t\t\t\t\t<li class=\"elementor-icon-list-item elementor-repeater-item-ef11192 elementor-inline-item\" itemprop=\"datePublished\">\n\t\t\t\t\t\t<a href=\"https:\/\/spinebigdata.com\/?m=20221028\">\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text elementor-post-info__item elementor-post-info__item--type-date\">\n\t\t\t\t\t\t\t\t\t\t<time>28 10 \u6708, 2022<\/time>\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<\/a>\n\t\t\t\t<\/li>\n\t\t\t\t<li class=\"elementor-icon-list-item elementor-repeater-item-b5b07d4 elementor-inline-item\">\n\t\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-icon\">\n\t\t\t\t\t\t\t\t<i aria-hidden=\"true\" class=\"far fa-clock\"><\/i>\t\t\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t\t<span class=\"elementor-icon-list-text elementor-post-info__item elementor-post-info__item--type-time\">\n\t\t\t\t\t\t\t\t\t\t<time>12:16 \u4e0b\u5348<\/time>\t\t\t\t\t<\/span>\n\t\t\t\t\t\t\t\t<\/li>\n\t\t\t\t<\/ul>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-7e66863d elementor-section-boxed elementor-section-height-default elementor-section-height-default\" data-id=\"7e66863d\" data-element_type=\"section\" data-e-type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-749bfa85\" data-id=\"749bfa85\" data-element_type=\"column\" data-e-type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t<div class=\"elementor-element elementor-element-8c4a383 elementor-widget elementor-widget-spacer\" data-id=\"8c4a383\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-51616887 elementor-widget elementor-widget-text-editor\" data-id=\"51616887\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t\t\t<div id=\"abstract\" class=\"abstract\"><h2 class=\"title\">Abstract<\/h2><div id=\"eng-abstract\" class=\"abstract-content selected\"><p>In recent years, exome sequencing (ES) has shown great utility in the diagnoses of Mendelian disorders. However, after rigorous filtering, a typical ES analysis still involves the interpretation of hundreds of variants, which greatly hinders the rapid identification of causative genes. Since the interpretations of ES data require comprehensive clinical analyses, taking clinical expertise into consideration can speed the molecular diagnoses of Mendelian disorders. To leverage clinical expertise to prioritize candidate genes, we developed PhenoApt, a phenotype-driven gene prioritization tool that allows users to assign a customized weight to each phenotype, via a machine-learning algorithm. Using the ability to rank causative genes in top-10 lists as an evaluation metric, baseline analysis demonstrated that PhenoApt outperformed previous phenotype-driven gene prioritization tools by a relative increase of 22.7%-140.0% in three independent, real-world, multi-center cohorts (cohort 1, n = 185; cohort 2, n = 784; and cohort 3, n = 208). Additional trials showed that, by adding weights to clinical indications, which should be explained by the causative gene, PhenoApt performance was improved by a relative increase of 37.3% in cohort 2 (n = 471) and 21.4% in cohort 3 (n = 208). Moreover, PhenoApt could assign an intrinsic weight to each phenotype based on the likelihood of its being a Mendelian trait using term frequency-inverse document frequency techniques. When clinical indications were assigned with intrinsic weights, PhenoApt performance was improved by a relative increase of 23.7% in cohort 2 and 15.5% in cohort 3. For the integration of PhenoApt into clinical practice, we developed a user-friendly website and a command-line tool.<\/p><\/div><p><strong class=\"sub-title\">Keywords:\u00a0<\/strong>Mendelian disorders; data analysis; exome sequencing; gene prioritization; machine learning; phenotype-driven analysis.<\/p><\/div>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-ab1ecab elementor-blockquote--skin-border elementor-widget elementor-widget-blockquote\" data-id=\"ab1ecab\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"blockquote.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<blockquote class=\"elementor-blockquote\">\n\t\t\t<p class=\"elementor-blockquote__content\">\n\t\t\t\tChen Z, Zheng Y, Yang Y, et al. PhenoApt leverages clinical expertise to prioritize candidate genes via machine learning. Am J Hum Genet. 2022;109(2):270-281. doi:10.1016\/j.ajhg.2021.12.008\t\t\t<\/p>\n\t\t\t\t\t<\/blockquote>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-60e77d52 elementor-widget elementor-widget-spacer\" data-id=\"60e77d52\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-601d8c30 elementor-widget elementor-widget-heading\" data-id=\"601d8c30\" data-element_type=\"widget\" data-e-type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">\u66f4\u591a\u65b0\u95fb<\/h2>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-b3cd89 elementor-grid-2 elementor-posts--align-center elementor-grid-tablet-2 elementor-grid-mobile-1 elementor-posts--thumbnail-top elementor-card-shadow-yes elementor-posts__hover-gradient elementor-widget elementor-widget-posts\" data-id=\"b3cd89\" data-element_type=\"widget\" data-e-type=\"widget\" data-settings=\"{&quot;cards_columns&quot;:&quot;2&quot;,&quot;cards_row_gap&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;30&quot;,&quot;sizes&quot;:[]},&quot;cards_columns_tablet&quot;:&quot;2&quot;,&quot;cards_columns_mobile&quot;:&quot;1&quot;,&quot;cards_row_gap_tablet&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]},&quot;cards_row_gap_mobile&quot;:{&quot;unit&quot;:&quot;px&quot;,&quot;size&quot;:&quot;&quot;,&quot;sizes&quot;:[]}}\" data-widget_type=\"posts.cards\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<div class=\"elementor-posts-container elementor-posts elementor-posts--skin-cards elementor-grid\" role=\"list\">\n\t\t\t\t<article class=\"elementor-post elementor-grid-item post-1750 post type-post status-publish format-standard has-post-thumbnail hentry category-10\" role=\"listitem\">\n\t\t\t<div class=\"elementor-post__card\">\n\t\t\t\t<a class=\"elementor-post__thumbnail__link\" href=\"https:\/\/spinebigdata.com\/?p=1750\" tabindex=\"-1\" ><div class=\"elementor-post__thumbnail\"><img decoding=\"async\" width=\"300\" height=\"131\" src=\"https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/640-1-300x131.png\" class=\"attachment-medium size-medium wp-image-1748\" alt=\"\" srcset=\"https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/640-1-300x131.png 300w, https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/640-1-1024x447.png 1024w, https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/640-1-768x335.png 768w, https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/640-1.png 1080w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/div><\/a>\n\t\t\t\t<div class=\"elementor-post__badge\">\u53d1\u8868\u6587\u7ae0<\/div>\n\t\t\t\t<div class=\"elementor-post__text\">\n\t\t\t\t<h3 class=\"elementor-post__title\">\n\t\t\t<a href=\"https:\/\/spinebigdata.com\/?p=1750\" >\n\t\t\t\t\u534f\u548c\u9aa8\u79d1\u56e2\u961f\u5728JAMA Pediatrics\u53d1\u8868\u77ee\u5c0f\u961f\u5217\u5206\u5b50\u8bca\u65ad\u7387\u76f8\u5173\u7814\u7a76\u6210\u679c\t\t\t<\/a>\n\t\t<\/h3>\n\t\t\t\t<div class=\"elementor-post__excerpt\">\n\t\t\t<p>2023\u5e749\u670811\u65e5\uff0c\u56fd\u9645\u8457\u540d\u6742\u5fd7JAMA Ped<\/p>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-post__meta-data\">\n\t\t\t\t\t<span class=\"elementor-post-author\">\n\t\t\tcaijihao\t\t<\/span>\n\t\t\t\t<span class=\"elementor-post-date\">\n\t\t\t2024\u5e74 3\u6708 21\u65e5\t\t<\/span>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/article>\n\t\t\t\t<article class=\"elementor-post elementor-grid-item post-1700 post type-post status-publish format-standard has-post-thumbnail hentry category-10\" role=\"listitem\">\n\t\t\t<div class=\"elementor-post__card\">\n\t\t\t\t<a class=\"elementor-post__thumbnail__link\" href=\"https:\/\/spinebigdata.com\/?p=1700\" tabindex=\"-1\" ><div class=\"elementor-post__thumbnail\"><img fetchpriority=\"high\" decoding=\"async\" width=\"300\" height=\"172\" src=\"https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/\u622a\u5c4f2024-03-21-15.52.49-300x172.png\" class=\"attachment-medium size-medium wp-image-1711\" alt=\"\" srcset=\"https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/\u622a\u5c4f2024-03-21-15.52.49-300x172.png 300w, https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/\u622a\u5c4f2024-03-21-15.52.49-1024x586.png 1024w, https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/\u622a\u5c4f2024-03-21-15.52.49-768x440.png 768w, https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/\u622a\u5c4f2024-03-21-15.52.49-1536x879.png 1536w, https:\/\/spinebigdata.com\/wp-content\/uploads\/2024\/03\/\u622a\u5c4f2024-03-21-15.52.49.png 1768w\" sizes=\"(max-width: 300px) 100vw, 300px\" \/><\/div><\/a>\n\t\t\t\t<div class=\"elementor-post__badge\">\u53d1\u8868\u6587\u7ae0<\/div>\n\t\t\t\t<div class=\"elementor-post__text\">\n\t\t\t\t<h3 class=\"elementor-post__title\">\n\t\t\t<a href=\"https:\/\/spinebigdata.com\/?p=1700\" >\n\t\t\t\t\u8bfe\u9898\u7ec4\u5728\u300aNat Commun\u300b\u53d1\u8868\u5148\u5929\u6027\u810a\u67f1\u7578\u5f62\u53d1\u75c5\u673a\u5236\u7814\u7a76\u65b9\u9762\u7814\u7a76\t\t\t<\/a>\n\t\t<\/h3>\n\t\t\t\t<div class=\"elementor-post__excerpt\">\n\t\t\t<p>\u5728\u56fd\u5bb6\u81ea\u7136\u79d1\u5b66\u57fa\u91d1\u9879\u76ee\uff08\u6279\u51c6\u53f7\uff1a82072391\u3001<\/p>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-post__meta-data\">\n\t\t\t\t\t<span class=\"elementor-post-author\">\n\t\t\tcaijihao\t\t<\/span>\n\t\t\t\t<span class=\"elementor-post-date\">\n\t\t\t2024\u5e74 3\u6708 21\u65e5\t\t<\/span>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/article>\n\t\t\t\t<\/div>\n\t\t\n\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Abstract In recent years, exome sequencing (ES) has sho [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":115,"comment_status":"open","ping_status":"open","sticky":false,"template":"elementor_header_footer","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[],"class_list":["post-971","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-10"],"_links":{"self":[{"href":"https:\/\/spinebigdata.com\/index.php?rest_route=\/wp\/v2\/posts\/971","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/spinebigdata.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/spinebigdata.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/spinebigdata.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/spinebigdata.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=971"}],"version-history":[{"count":23,"href":"https:\/\/spinebigdata.com\/index.php?rest_route=\/wp\/v2\/posts\/971\/revisions"}],"predecessor-version":[{"id":995,"href":"https:\/\/spinebigdata.com\/index.php?rest_route=\/wp\/v2\/posts\/971\/revisions\/995"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/spinebigdata.com\/index.php?rest_route=\/wp\/v2\/media\/115"}],"wp:attachment":[{"href":"https:\/\/spinebigdata.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=971"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/spinebigdata.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=971"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/spinebigdata.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=971"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}