{"id":79179,"date":"2026-05-06T17:52:12","date_gmt":"2026-05-06T15:52:12","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=79179"},"modified":"2026-05-06T17:52:17","modified_gmt":"2026-05-06T15:52:17","slug":"scientists-uncover-thousands-of-new-proteins-in-dark-proteome","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science-technology\/scientists-uncover-thousands-of-new-proteins-in-dark-proteome\/","title":{"rendered":"Scientists uncover thousands of new proteins in \u2018dark proteome&#8217;"},"content":{"rendered":"\n<p>In a collaborative effort, scientists in the TransCODE consortium reveal more than 1,700 new proteins that could have implications for human diseases, including cancer. These tiny proteins were found in what\u2019s called the \u2018dark proteome\u2019, a portion of the human genome historically thought to be nonfunctional.\u00a0<\/p>\n\n\n\n<p>The TransCODE consortium is a collaboration between experts at EMBL\u2019s European Bioinformatics Institute (EMBL-EBI), the Princess M\u00e1xima Center for Pediatric Oncology in the Netherlands, the University of Michigan, the Institute for Systems Biology in Seattle, and the Massachusetts Institute of Technology (MIT).<\/p>\n\n\n\n<p>In the study, <a href=\"https:\/\/www.nature.com\/articles\/s41586-026-10459-x\">published in <em>Nature<\/em><\/a>, the scientists looked at 7,264 non-canonical Open Reading Frames (ncORFs) and found that around 25% of them produce small, protein-like molecules. The team coined the term \u2018peptidein\u2019 for this new category of microproteins. All data about these new proteins have been made publicly available to accelerate research worldwide.<\/p>\n\n\n\n<p>\u201cWhat we\u2019re now seeing is a vast set of protein-like molecules that were effectively invisible before,&#8221; said Jonathan Mudge, co-first author on the paper and Annotation Project Leader at EMBL-EBI. \u201cIn a sense, we\u2019ve been looking at biology through an incomplete lens.\u201d<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">A new group of proteins called peptideins<\/h2>\n\n\n\n<p>The consortium will add peptideins to reference databases, such as <a href=\"https:\/\/www.gencodegenes.org\/\">GENCODE<\/a>, <a href=\"https:\/\/www.uniprot.org\/\">UniProt<\/a>, and <a href=\"https:\/\/peptideatlas.org\/\">PeptideAtlas.<\/a> Due to their small size, ncORFs and the proteins they encode have largely been absent from these databases. \u201cWe introduced the term \u2018peptidein\u2019 as a way to bring these molecules out of the shadows and into reference annotation,\u201d said Mudge.<\/p>\n\n\n\n<p>These data will help researchers get a more complete picture of biological processes in and around different types of cells. Scientists could, for example, identify more precise targets for immunotherapy, or compare candidates for new therapies and analyse data more effectively. The consortium intends to continue making peptidein data open as soon as it becomes available.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Implications for cancer treatment and beyond<\/h2>\n\n\n\n<p>As many of the newly detected peptideins are found on immune cell surfaces, they could be potential targets for cancer immunotherapy. \u201cCancer cells express high levels of these molecules, making them a potential new source of biomarkers and therapeutic targets,\u201d said Mudge. A number of peptideins are already under development as drug targets.&nbsp;<\/p>\n\n\n\n<p>To find out whether any of the peptideins are essential for cell survival, the consortium used CRISPR gene-editing screens. A gene called OLMALINC, which was previously thought to be noncoding, stood out. When this peptidein was made inactive, 85% of the 485 cancer cell lines tested showed impaired survival.<\/p>\n\n\n\n<p>They also found that it plays a role in cell division and DNA damage response. Despite these promising findings, a role for the OLMALINC peptidein in normal, healthy cells remains unclear.<\/p>\n\n\n\n<p>Previous work by members of the consortium has already identified a peptidein that plays an essential role in medulloblastoma, a particularly aggressive form of childhood brain cancer. With the new classification, the team hopes to encourage similar investigations into other diseases.<\/p>\n\n\n\n<p><em>This press release was adapted from the <\/em><a href=\"https:\/\/www.prinsesmaximacentrum.nl\/en\/news\/thousands-of-previously-unknown-proteins-discovered\"><em>full press release published on the Princess M\u00e1xima website.<\/em><\/a><\/p>\n\n\n\n<article class=\"vf-card vf-card--brand vf-card--bordered vf-u-margin__bottom--800\" default>\n  <div class=\"vf-card__content | vf-stack vf-stack--400\">\n      <h3 class=\"vf-card__heading\">\n      Funding    <\/h3>\n                <p class=\"vf-card__text\">The study was conducted by the TransCODE consortium, an international collaboration of more than 60 researchers from over 30 institutions worldwide. The consortium is co-led by the Princess M\u00e1xima Center for pediatric oncology in the Netherlands, the University of Michigan Medical School, EMBL\u2019s European Bioinformatics Institute (EMBL-EBI) in Hinxton (UK), and the Institute for Systems Biology in Seattle. The consortium continues its work and collaborates with other dark proteome initiatives, such as the recently awarded Cancer Grand Challenge to Team ILLUMINE. <br \/><br \/>\r\n\r\nThe study was supported by funders including the US National Institutes of Health, the National Science Foundation, Oncode Accelerator (a Dutch National Growth Fund program) and the European Union\u2019s Marie-Sk\u0142odowska-Curie program.<\/p>\n      <\/div>\n<\/article>\n\n","protected":false},"excerpt":{"rendered":"<p>An international consortium has found over 1,700 new proteins from noncoding DNA, many of which show potential as targets for cancer immunotherapy.<\/p>\n","protected":false},"author":189,"featured_media":79273,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[17591,11056],"tags":[19689,36],"embl_taxonomy":[2906,10044,18909],"class_list":["post-79179","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science-technology","category-technology-and-innovation","tag-dark-proteome","tag-embl-ebi","embl_taxonomy-embl-ebi","embl_taxonomy-eukaryotic-annotation","embl_taxonomy-fergal-martin"],"acf":{"vfwp-news_embl_taxonomy":[2906,10044,18909],"featured":true,"show_featured_image":false,"field_target_display":"both","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>An international consortium has found over 1,700 new proteins from noncoding DNA, many of which show potential as targets for cancer immunotherapy<\/p>\n","related_links":false,"source_article":false,"in_this_article":false,"press_contact":"None","article_translations":false,"languages":""},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"b14d3f13-5670-44fb-8970-e54dfd9c921a\";i:1;s:36:\"89e00fee-87f4-482e-a801-4c3548bb6a58\";i:2;s:36:\"a99d1a7c-ca83-4c00-ab61-d082d3e41ce3\";}","parents":[],"name":["EMBL-EBI"],"slug":"embl-ebi","description":"Where &gt; All EMBL sites &gt; EMBL-EBI"},{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"18699e63-ed43-40c6-8d1c-203db7ed72ee\";i:2;s:36:\"d20e13f1-14d2-4955-9467-c33b02fcdf13\";}","parents":[],"name":["Eukaryotic Annotation"],"slug":"eukaryotic-annotation","description":"What &gt; EMBL-EBI Services &gt; Eukaryotic Annotation"},{"uuid":"a:2:{i:0;s:36:\"4428d1fd-441a-4d6d-a1c5-5dcf5665f213\";i:1;s:36:\"21183a46-35bd-4372-9973-551de92df30f\";}","parents":[],"name":["Fergal Martin"],"slug":"fergal-martin","description":"Who &gt; Fergal Martin"}],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Scientists uncover thousands of new proteins in \u2018dark proteome&#039; | EMBL<\/title>\n<meta name=\"description\" content=\"An international consortium has found over 1,700 new proteins from noncoding DNA, many of which show potential as targets for cancer immunotherapy\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.embl.org\/news\/science-technology\/scientists-uncover-thousands-of-new-proteins-in-dark-proteome\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Scientists uncover thousands of new proteins in \u2018dark proteome&#039; 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