{"id":682542,"date":"2025-08-01T04:40:17","date_gmt":"2025-08-01T01:40:17","guid":{"rendered":"https:\/\/buradabiliyorum.com\/en\/new-ai-tool-illuminates-dark-side-of-the-human-genome\/"},"modified":"2025-08-01T04:40:17","modified_gmt":"2025-08-01T01:40:17","slug":"new-ai-tool-illuminates-dark-side-of-the-human-genome","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/new-ai-tool-illuminates-dark-side-of-the-human-genome\/","title":{"rendered":"New AI tool illuminates &#8216;dark side&#8217; of the human genome"},"content":{"rendered":"<div id=\"ez-toc-container\" class=\"ez-toc-v2_0_85 counter-hierarchy ez-toc-counter ez-toc-custom ez-toc-container-direction\">\n<p class=\"ez-toc-title\" style=\"cursor:inherit\">Table of Contents<\/p>\n<label for=\"ez-toc-cssicon-toggle-item-6a39f17b853bd\" class=\"ez-toc-cssicon-toggle-label\"><span class=\"\"><span class=\"eztoc-hide\" style=\"display:none;\">Toggle<\/span><span class=\"ez-toc-icon-toggle-span\"><svg style=\"fill: #dd3333;color:#dd3333\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" class=\"list-377408\" width=\"20px\" height=\"20px\" viewBox=\"0 0 24 24\" fill=\"none\"><path d=\"M6 6H4v2h2V6zm14 0H8v2h12V6zM4 11h2v2H4v-2zm16 0H8v2h12v-2zM4 16h2v2H4v-2zm16 0H8v2h12v-2z\" fill=\"currentColor\"><\/path><\/svg><svg style=\"fill: #dd3333;color:#dd3333\" class=\"arrow-unsorted-368013\" xmlns=\"http:\/\/www.w3.org\/2000\/svg\" width=\"10px\" height=\"10px\" viewBox=\"0 0 24 24\" version=\"1.2\" baseProfile=\"tiny\"><path d=\"M18.2 9.3l-6.2-6.3-6.2 6.3c-.2.2-.3.4-.3.7s.1.5.3.7c.2.2.4.3.7.3h11c.3 0 .5-.1.7-.3.2-.2.3-.5.3-.7s-.1-.5-.3-.7zM5.8 14.7l6.2 6.3 6.2-6.3c.2-.2.3-.5.3-.7s-.1-.5-.3-.7c-.2-.2-.4-.3-.7-.3h-11c-.3 0-.5.1-.7.3-.2.2-.3.5-.3.7s.1.5.3.7z\"\/><\/svg><\/span><\/span><\/label><input type=\"checkbox\"  id=\"ez-toc-cssicon-toggle-item-6a39f17b853bd\" checked aria-label=\"Toggle\" \/><nav><ul class='ez-toc-list ez-toc-list-level-1 ' ><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-1\" href=\"https:\/\/buradabiliyorum.com\/en\/new-ai-tool-illuminates-dark-side-of-the-human-genome\/#More_about_microproteins\" >More about microproteins<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-2\" href=\"https:\/\/buradabiliyorum.com\/en\/new-ai-tool-illuminates-dark-side-of-the-human-genome\/#How_ShortStop_works\" >How ShortStop works<\/a><\/li><li class='ez-toc-page-1 ez-toc-heading-level-2'><a class=\"ez-toc-link ez-toc-heading-3\" href=\"https:\/\/buradabiliyorum.com\/en\/new-ai-tool-illuminates-dark-side-of-the-human-genome\/#ShortStop_spots_microprotein_associated_with_lung_cancer\" >ShortStop spots microprotein associated with lung cancer<\/a><\/li><\/ul><\/nav><\/div>\n<div>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2025\/new-ai-tool-illuminate-1.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2025\/new-ai-tool-illuminate-1.jpg\" data-sub-html=\"Cells express a novel ShortStop-predicted microprotein (green), with cell nuclei stained blue. The pattern suggests microproteins are localized either in endosomes, which are organelles responsible for sorting and transporting cellular cargo, or in lysosomes, which are organelles that collect and remove cellular waste. Credit: Salk Institute\">\n<figure class=\"article-img\">\n            <img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/scx1.b-cdn.net\/csz\/news\/800a\/2025\/new-ai-tool-illuminate-1.jpg\" alt=\"New AI tool illuminates &quot;dark side&quot; of the human genome\" title=\"Cells express a novel ShortStop-predicted microprotein (green), with cell nuclei stained blue. The pattern suggests microproteins are localized either in endosomes, which are organelles responsible for sorting and transporting cellular cargo, or in lysosomes, which are organelles that collect and remove cellular waste. Credit: Salk Institute\" width=\"800\" height=\"530\"\/><figcaption class=\"text-darken text-low-up text-truncate-js text-truncate mt-3\">\n                Cells express a novel ShortStop-predicted microprotein (green), with cell nuclei stained blue. The pattern suggests microproteins are localized either in endosomes, which are organelles responsible for sorting and transporting cellular cargo, or in lysosomes, which are organelles that collect and remove cellular waste. Credit: Salk Institute<br \/>\n            <\/figcaption><\/figure>\n<\/p><\/div>\n<\/div>\n<p>Proteins sustain life as we know it, serving many important structural and functional roles throughout the body. But these large molecules have cast a long shadow over a smaller subclass of proteins called microproteins.<\/p>\n<p>Microproteins have been lost in the 99% of DNA disregarded as &#8220;noncoding&#8221;\u2014hiding in vast, dark stretches of unexplored genetic code. But despite being small and elusive, their impact may be just as big as larger proteins.<\/p>\n<p>Salk Institute scientists are now exploring the mysterious dark side of the genome in search of microproteins. With their new tool ShortStop, researchers can probe genetic databases and identify DNA stretches in the genome that likely code for microproteins.<\/p>\n<p>Importantly, ShortStop also predicts which microproteins are most likely to be biologically relevant, saving time and money in the search for microproteins involved in health and disease.<\/p>\n<p>ShortStop shines a new light on existing datasets, spotlighting microproteins formerly impossible to find. In fact, the Salk team has already used the tool to analyze a lung cancer dataset to find 210 entirely new microprotein candidates\u2014with one standout validated microprotein\u2014that may make good therapeutic targets in the future.<\/p>\n<p>The findings were published in <i>BMC Methods<\/i>.<\/p>\n<p>&#8220;Most of the proteins in our body are well known, but recent discoveries suggest we&#8217;ve been missing thousands of small, hidden proteins\u2014called microproteins\u2014coded by overlooked regions of our genome,&#8221; says senior author Alan Saghatelian, professor and holder of the Dr. Frederik Paulsen Chair at Salk.<\/p>\n<p>&#8220;For a long time, scientists only really studied the regions of DNA that coded for large proteins and dismissed the rest as &#8216;junk DNA,&#8217; but we&#8217;re now learning that these other regions are actually very important, and the microproteins they produce could play critical roles in regulating health and disease.&#8221;<\/p>\n<h2><span class=\"ez-toc-section\" id=\"More_about_microproteins\"><\/span>More about microproteins<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>It is difficult to detect and catalog microproteins, owing mostly to their size. Compared to standard proteins that can range from hundreds to thousands of amino acids long, microproteins typically contain fewer than 150 amino acids, making them harder to detect using standard protein analysis methods.<\/p>\n<p>Therefore, instead of searching for the microproteins themselves, scientists search large, publicly available datasets for the DNA sequences that make them.<\/p>\n<p>Scientists have now learned that certain stretches of DNA called small open reading frames (smORFs) can contain the instructions for making microproteins. Current experimental methods have already cataloged thousands of smORFs, but these tools remain time-consuming and expensive.<\/p>\n<p>Furthermore, their inability to separate potentially functional microproteins from nonfunctional microproteins has stalled their discovery and characterization.<\/p>\n<h2><span class=\"ez-toc-section\" id=\"How_ShortStop_works\"><\/span>How ShortStop works<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>Not all smORFs translate to biologically meaningful microproteins. Existing methods can&#8217;t discriminate between functional and nonfunctional microprotein-generating smORFs. This means that scientists must independently test each microprotein to determine whether it is functional or not.<\/p>\n<p>ShortStop radically alters this workflow, optimizing smORF discovery by sorting microproteins into functional and nonfunctional categories. The key to ShortStop&#8217;s two-class sorting is how it&#8217;s trained as a machine learning system.<\/p>\n<div class=\"ads w-100 my-4 article-main__more bg-light p-3 border\" aria-hidden=\"true\">\n<p class=\"mb-3\">\n        Discover the latest in <a href=\"https:\/\/buradabiliyorum.com\/en\/category\/sciencee\/\" data-internallinksmanager029f6b8e52c=\"5\" title=\"Science\" target=\"_blank\" rel=\"noopener\">science<\/a>, tech, and space with over <strong>100,000 subscribers<\/strong> who rely on Phys.org for daily insights.<br \/>\n        Sign up for our <a rel=\"nofollow\" target=\"_blank\" href=\"https:\/\/sciencex.com\/help\/newsletter\/\" target=\"_blank\">free newsletter<\/a> and get updates on breakthroughs,<br \/>\n        innovations, and research that matter\u2014<strong>daily or weekly<\/strong>.\n    <\/p>\n<\/div>\n<p>Its training relies on a negative control dataset of computer-generated random smORFs. ShortStop compares found smORFs against these decoys to quickly decide whether a new smORF is likely to be functional or nonfunctional.<\/p>\n<p>ShortStop cannot definitively say whether a smORF will code for a biologically relevant microprotein, but this two-class system narrows down the experimental pool immensely. Now researchers can spend less time manually sorting through datasets and failing at the bench.<\/p>\n<p>When the researchers <a href=\"https:\/\/buradabiliyorum.com\/en\/category\/download-scripts-themes-apps\/\" data-internallinksmanager029f6b8e52c=\"9\" title=\"Download Scripts &amp; Themes &amp; Apps\" target=\"_blank\" rel=\"noopener\">app<\/a>lied ShortStop to a previously published smORF dataset, they identified 8% as likely functional microproteins, prioritizing them for targeted follow-up.<\/p>\n<p>This accelerates microprotein characterization by filtering out sequences unlikely to have biological relevance. ShortStop could also identify microproteins that were overlooked by other methods, including one that was validated by being detected in human cells and tissues.<\/p>\n<p>&#8220;What makes ShortStop especially powerful is that it works with common data types, like RNA sequencing datasets, which many labs already use,&#8221; says first author Brendan Miller, a postdoctoral researcher in Saghatelian&#8217;s lab.<\/p>\n<p>&#8220;This means we can now search for microproteins across healthy and diseased tissues at scale, which will reveal new insights into human biology and unlock new paths for diagnosing and treating diseases, such as cancer and Alzheimer&#8217;s disease.&#8221;<\/p>\n<div class=\"article-gallery lightGallery\">\n<div data-thumb=\"https:\/\/scx1.b-cdn.net\/csz\/news\/tmb\/2025\/new-ai-tool-illuminate.jpg\" data-src=\"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2025\/new-ai-tool-illuminate.jpg\" data-sub-html=\"Brendan Miller (left) and Alan Saghatelian (right) stand in their lab, while ShortStop runs on the desktop beside them. Credit: Salk Institute\">\n<figure class=\"article-img text-center\">\n            <img decoding=\"async\" src=\"https:\/\/scx1.b-cdn.net\/csz\/news\/800a\/2025\/new-ai-tool-illuminate.jpg\" alt=\"New AI tool illuminates &quot;dark side&quot; of the human genome\" title=\"Brendan Miller (left) and Alan Saghatelian (right) stand in their lab, while ShortStop runs on the desktop beside them. Credit: Salk Institute\"\/><figcaption class=\"text-left text-darken text-truncate text-low-up mt-3\">\n                Brendan Miller (left) and Alan Saghatelian (right) stand in their lab, while ShortStop runs on the desktop beside them. Credit: Salk Institute<br \/>\n            <\/figcaption><\/figure>\n<\/p><\/div>\n<\/div>\n<h2><span class=\"ez-toc-section\" id=\"ShortStop_spots_microprotein_associated_with_lung_cancer\"><\/span>ShortStop spots microprotein associated with lung cancer<span class=\"ez-toc-section-end\"><\/span><\/h2>\n<p>The researchers have already used ShortStop to identify a microprotein that was upregulated in lung cancer tumors. They analyzed genetic data from human lung tumors and adjacent normal tissue to create a list of potential functional smORFs.<\/p>\n<p>Among the smORFs ShortStop found, one stood out\u2014it was expressed more in tumor tissue than normal tissue, suggesting it may serve as a biomarker or functional microprotein for lung cancer.<\/p>\n<p>The identification of this lung cancer-related microprotein demonstrates the value of ShortStop and machine learning to prioritize candidates for future research and therapeutic development.<\/p>\n<p>&#8220;There&#8217;s so much data that already exists that we can now process with ShortStop to find novel microproteins associated with health and disease, stretching from Alzheimer&#8217;s to obesity and beyond,&#8221; says Saghatelian.<\/p>\n<p>&#8220;My team is really good at making methods, and with data from other Salk faculty members, we can integrate these methods and accelerate the science.&#8221;<\/p>\n<div class=\"article-main__more p-4\">\n<p><strong>More information:<\/strong><br \/>\n\t\t\t\t\t\t\t\t\t\t\t\tShortStop: A machine learning framework for microprotein discovery, <i>BMC Methods<\/i> (2025). <a rel=\"nofollow\" target=\"_blank\" data-doi=\"1\" href=\"https:\/\/dx.doi.org\/10.1186\/s44330-025-00037-4\" target=\"_blank\">DOI: 10.1186\/s44330-025-00037-4<\/a><\/p>\n<\/div>\n<div class=\"d-inline-block text-medium mt-4\">\n<p>\n\t\t\t\t\t\t\t\t\t\t\t\t\tProvided by<br \/>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\tSalk Institute<br \/>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<a rel=\"nofollow\" target=\"_blank\" class=\"icon_open\" href=\"http:\/\/www.salk.edu\/\" target=\"_blank\" rel=\"nofollow\"><br \/>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<svg>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<use href=\"https:\/\/phys.b-cdn.net\/tmpl\/v6\/img\/svg\/sprite.svg#icon_open\" x=\"0\" y=\"0\"\/>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/svg><br \/>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/a>\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t<\/p>\n<\/p><\/div>\n<p>\t\t\t\t\t\t\t\t\t\t<!-- print only --><\/p>\n<div class=\"d-none d-print-block\">\n<p>\n\t\t\t\t\t\t\t\t\t\t\t\t<strong>Citation<\/strong>:<br \/>\n\t\t\t\t\t\t\t\t\t\t\t\tNew AI tool illuminates &#8216;dark side&#8217; of the human genome (2025, July 31)<br \/>\n\t\t\t\t\t\t\t\t\t\t\t\tretrieved 31 July 2025<br \/>\n\t\t\t\t\t\t\t\t\t\t\t\tfrom https:\/\/phys.org\/<a href=\"https:\/\/buradabiliyorum.com\/en\/category\/news\/\" data-internallinksmanager029f6b8e52c=\"2\" title=\"News\" target=\"_blank\" rel=\"noopener\">news<\/a>\/2025-07-ai-tool-illuminates-dark-side.html\n\t\t\t\t\t\t\t\t\t\t\t <\/p>\n<p>\n\t\t\t\t\t\t\t\t\t\t\t This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no<br \/>\n\t\t\t\t\t\t\t\t\t\t\t part may be reproduced without the written permission. The content is provided for information purposes only.\n\t\t\t\t\t\t\t\t\t\t\t <\/p>\n<\/p><\/div>\n<\/p><\/div>\n<p><script id=\"facebook-jssdk\" async=\"\" src=\"https:\/\/connect.facebook.net\/en_US\/sdk.js\"><\/script><\/p>\n<blockquote><p><strong><span style=\"color: #ff6600;\">If you liked the article, do not forget to share it with your friends. Follow us on\u00a0<span style=\"color: #ff0000;\"><a style=\"color: #ff0000;\" href=\"https:\/\/news.google.com\/publications\/CAAqBwgKMN63nwsw68G3Aw\" target=\"_blank\" rel=\"nofollow noopener noreferrer\">Google News<\/a><\/span>\u00a0too, click on the star and choose us from your favorites.<\/span><\/strong><\/p><\/blockquote>\n<blockquote>\n<p style=\"text-align: center;\"><strong>If you want to read more Like this articles, you can visit our <span style=\"color: #ff9900;\"><a style=\"color: #ff9900;\" href=\"https:\/\/buradabiliyorum.com\/en\/category\/sciencee\/\" target=\"_blank\" >Science category.<\/a><\/span><\/strong><\/p>\n<\/blockquote>\n<p><span style=\"color: black;\"><a style=\"color: #ff9900;\" href=\"https:\/\/phys.org\/news\/2025-07-ai-tool-illuminates-dark-side.html\" target=\"_blank\" >Source<\/a><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cells express a novel ShortStop-predicted microprotein (green), with cell nuclei stained blue. The pattern suggests microproteins are localized either in endosomes, which are organelles responsible for sorting and transporting cellular cargo, or in lysosomes, which are organelles that collect and remove cellular waste. Credit: Salk Institute Proteins sustain life as we know it, serving many&#8230;<\/p>\n","protected":false},"author":1,"featured_media":682543,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"fifu_image_url":"https:\/\/scx2.b-cdn.net\/gfx\/news\/hires\/2025\/new-ai-tool-illuminate-1.jpg","fifu_image_alt":"","footnotes":""},"categories":[16],"tags":[],"class_list":["post-682542","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-sciencee"],"_links":{"self":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/682542","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/comments?post=682542"}],"version-history":[{"count":0,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/posts\/682542\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media\/682543"}],"wp:attachment":[{"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/media?parent=682542"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/categories?post=682542"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/buradabiliyorum.com\/en\/wp-json\/wp\/v2\/tags?post=682542"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}