CINXE.COM

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mutations. With CRISPR gene-editing technology, a select few of these mutations might have therapeutic potential. However, proving it would mean many thousands of hours of lab work. Just figuring out which ones are worth exploring further would take a lot of time and money. 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href="https://www.cshl.edu/news-stand/">Newsstand</a> / <a href="https://www.cshl.edu/news-stand/cshl-stories/">CSHL Stories and Media</a></span></p> </div> </div> <article id="post-71483" class="post-71483 post type-post status-publish format-standard has-post-thumbnail hentry category-research tag-artificial-intelligence tag-crispr tag-genomics tag-peter-koo tag-quantitative-biology">  <header> <div class="row"> <div class="col-lg-10 col-lg-offset-1 col-lg-offset-right-1 col-md-12 col-sm-12 col-xs-12"> <h1>Is CREME AI’s answer to CRISPR?</h1> </div> </div> </header>  <div class="row area-start"> <div class="col-lg-10 col-lg-offset-1 col-lg-offset-right-1 col-md-12 col-sm-12 col-xs-12"> <img class="img-responsive" src="https://www.cshl.edu/wp-content/uploads/2024/08/CREME_artificial_intelligence_toolkit.jpg" alt="image of artificial intelligence toolkit" /><figcaption class="cshl-post-caption">CREME, the latest artificial intelligence toolkit from CSHL Assistant Professor Peter Koo’s laboratory, allows geneticists to simulate thousands of experiments in a virtual laboratory. AI-generated image: © Muhammad - stock.adobe.com</figcaption></div> </div> <div class="entry-content"> <div class="row"> <div class="col-lg-10 col-lg-offset-1 col-lg-offset-right-1 col-md-12 col-sm-12 col-xs-12"> <div class="entry-meta article-date top-margin-20 bottom-margin-25"><em> Read time 3 minutes | <span class="posted-on"><time class="entry-date published" datetime="Monday, 16 September 2024">Monday, 16 September 2024</time></span> </em> <div class='social-share-wrapper'><span class='email'><a href='mailto:?Subject=Is CREME AI’s answer to CRISPR?&Body=https://www.cshl.edu/is-creme-ais-answer-to-crispr/'><i class='fa-solid fa-square-envelope fa-3x social-share-icon ag-mail' aria-hidden='true'><span class='sr-only'>email envelop icon</span></i></a></span><span class='twitter'><a target='_blank' href='https://twitter.com/share?url=https://www.cshl.edu/is-creme-ais-answer-to-crispr/'><i class='fa-brands fa-square-x-twitter fa-3x social-share-icon x-twitter' aria-hidden='true'><span class='sr-only'>twitter icon share button</span></i></a></span><span class='facebook'><a target='_blank' href='http://www.facebook.com/sharer.php?u=https://www.cshl.edu/is-creme-ais-answer-to-crispr/'><i class='fa-brands fa-square-facebook fa-3x social-share-icon ag-facebook' aria-hidden='true'><span class='sr-only'>facebook icon share button</span></i></a></span><span class='linkedin'><a target='_blank' href='http://www.linkedin.com/shareArticle?url=https://www.cshl.edu/is-creme-ais-answer-to-crispr/'><i class='fa-brands fa-linkedin fa-3x social-share-icon ag-linkedin' aria-hidden='true'><span class='sr-only'>linkedin icon share button</span></i></a></span><div class='clear'></div></div> </div> </div> </div>  <div class="row area-start"> <div class="col-lg-7 col-lg-offset-1 col-md-8 col-sm-12 col-xs-12"> <div class="hidden-lg hidden-md print-yes"> <div class="takeaway-box print-yes"> <h4 class="orange-font print-yes">The Takeaway</h4> <p class="print-yes">CREME is a virtual laboratory that allows scientists to simulate specific decreases in gene activity. It offers a powerful new tool for identifying and understanding important parts of the genome. And it could one day give scientists who don’t have access to real laboratories the power to make breakthrough discoveries.</p> </div> </div> <div class="printfriendly pf-button pf-button-content pf-alignleft"> <a href="#" rel="nofollow" onclick="window.print(); return false;" title="Printer Friendly, PDF & Email"> <img decoding="async" src="https://www.cshl.edu/wp-content/uploads/2023/03/print_pdf_icon.png" alt="Print Friendly, PDF & Email" class="pf-button-img" style="width: 124px;height: 36px;" /> </a> </div><p>Imagine you’re looking at millions upon millions of mysterious genetic mutations. With CRISPR gene-editing technology, a select few of these mutations <em>might</em> have therapeutic potential. However, proving it would mean many thousands of hours of lab work. Just figuring out which ones are worth exploring further would take a lot of time and money. But what if you could do it in the virtual realm with <a href="https://www.cshl.edu/finding-the-right-ai-for-you/">artificial intelligence</a>?</p> <p>CREME is a new AI-powered virtual laboratory invented by Cold Spring Harbor Laboratory (CSHL) Assistant Professor <a href="https://www.cshl.edu/research/faculty-staff/peter-koo/">Peter Koo</a> and his team. It allows geneticists to run thousands of virtual experiments with the click of a button. Now, scientists can use it to begin identifying and understanding key regions of the genome.</p> <p>The program is modeled after CRISPR interference (CRISPRi), a genetic perturbation technique based on CRISPR. CRISPRi allows biologists to turn down the activity of specific genes in a cell. CREME lets scientists make similar changes in the virtual genome and predicts their effects on gene activity. In other words, it’s almost like an AI version of CRISPRi. Koo explains:</p> <p><span class="soundcite" data-url="https://www.cshl.edu/wp-content/uploads/2024/08/Koo_CRISPRi.mp3">“In reality, CRISPRi is incredibly challenging to perform in the laboratory. And you’re limited by the number of perturbations and the scale. But since we’re doing all our perturbations [virtually], we can push the boundaries. And the scale of experiments that we performed is unprecedented—hundreds of thousands of perturbation experiments.”</span></p> <p>Koo and his team tested CREME on another AI-powered genome analysis tool called Enformer. They wanted to know how Enformer’s algorithm makes predictions about the genome. Questions like that are central to Koo’s work, he says.</p> <p><span class="soundcite" data-url="https://www.cshl.edu/wp-content/uploads/2024/08/Koo_big_powerful_models_predictions.mp3">“We have these big, powerful models. They’re quite compelling at taking DNA sequences and predicting gene expression. But we don’t really have any good ways of trying to understand what these models are learning. Presumably, they’re making accurate predictions because they’ve learned a lot of the rules about gene regulation, but we don’t actually know what their predictions are based off of.”</span></p> <p>With CREME, Koo’s team uncovered a series of genetic rules that Enformer learned while analyzing the genome. That insight may one day prove invaluable for <a href="https://www.cshl.edu/laying-the-groundwork-for-drug-discoveries/">drug discovery</a>. “Understanding the rules of gene regulation gives you more options for tuning gene expression levels in precise and predictable ways,” says Koo.</p> <p>With further fine-tuning, CREME may soon set geneticists on the path to discovering new therapeutic targets. Perhaps most impactfully, it may even give scientists who do not have access to a real laboratory the power to make these breakthroughs.</p> <p><strong>Written by</strong>: <a href="https://www.cshl.edu/author/sandoval/">Luis Sandoval</a>, <em>Communications Specialist</em> | <a href="mailto:sandova@cshl.edu">sandova@cshl.edu</a> | 516-367-6826</p><hr><section id="funding"><p class="bottom-margin-10"><strong>Funding</strong></p><div class="printfriendly pf-button pf-button-content pf-alignleft"> <a href="#" rel="nofollow" onclick="window.print(); return false;" title="Printer Friendly, PDF & Email"><br /> <img decoding="async" src="https://www.cshl.edu/wp-content/uploads/2023/03/print_pdf_icon.png" alt="Print Friendly, PDF & Email" class="pf-button-img" style="width: 124px;height: 36px;" /><br /> </a> </div> <p>National Human Genome Research Institute, National Institute of General Medical Sciences, Simons Center for Quantitative Biology, National Institutes of Health, NVIDIA GPU Grant Program</p> </section><section id="citation"><p class="bottom-margin-10"><strong>Citation</strong></p><div class="printfriendly pf-button pf-button-content pf-alignleft"> <a href="#" rel="nofollow" onclick="window.print(); return false;" title="Printer Friendly, PDF & Email"><br /> <img decoding="async" src="https://www.cshl.edu/wp-content/uploads/2023/03/print_pdf_icon.png" alt="Print Friendly, PDF & Email" class="pf-button-img" style="width: 124px;height: 36px;" /><br /> </a> </div> <p>Toneyan, S., <em>et al</em>., “Interpreting cis-regulatory Interactions from large-scale deep neural networks”, <em>Nature Genetics</em>, Sept 16, 2024. DOI: <a href="https://doi.org/10.1038/s41588-024-01923-3" target="_blank" rel="noopener">10.1038/s41588-024-01923-3</a></p> </section> <section> </section> <div class="textwidget custom-html-widget"><div id="newsletter" class="panel panel-cshl"> <div class="panel-heading"> <h4> Stay informed </h4> </div> <div class="panel-body"> <p>Sign up for our newsletter to get the latest discoveries, upcoming events, videos, podcasts, and a news roundup delivered straight to your inbox every month. </p> <p class="text-center"><a href="https://www.cshl.edu/news-stand/newsletter/" class="btn btn-lg btn-learn-more-ag-gold"><span class="fa fa-envelope"></span>   Newsletter Signup</a></p> </div></div></div> </div>  <div class="col-lg-3 col-md-4 col-lg-offset-right-1 col-sm-12 col-xs-12"> <div class="hidden-sm hidden-xs print-no"> <div class="takeaway-box"> <h3 class="news-story">The Takeaway</h3> <p>CREME is a virtual laboratory that allows scientists to simulate specific decreases in gene activity. It offers a powerful new tool for identifying and understanding important parts of the genome. And it could one day give scientists who don’t have access to real laboratories the power to make breakthrough discoveries.</p> </div> </div> <h3 class="news-story">Principal Investigator</h3><img class="img-responsive pi-headshot" alt ="Peter Koo" src="https://www.cshl.edu/wp-content/uploads/2022/02/Peter-Koo_profile.jpg"/><a href="https://www.cshl.edu/research/faculty-staff/peter-koo/"><h4>Peter Koo</h4></a> <p>Associate Professor<br/>Cancer Center Member<br>Ph.D., Yale University, 2015</p><h3>Tags</h3><div class="post-cloud"><a href="https://www.cshl.edu/tag/artificial-intelligence/" rel="tag">artificial intelligence</a> <a href="https://www.cshl.edu/tag/crispr/" rel="tag">CRISPR</a> <a href="https://www.cshl.edu/tag/genomics/" rel="tag">Genomics</a> <a href="https://www.cshl.edu/tag/peter-koo/" rel="tag">Peter Koo</a> <a href="https://www.cshl.edu/tag/quantitative-biology/" rel="tag">Quantitative Biology</a></div> <div>  </div>  </div> </article> <div class='yarpp yarpp-related yarpp-related-widget yarpp-template-yarpp-template-cshl-related-content'> <style> .related-content-tile { background: #ffffff; border: 1px solid rgb(212,212,212); height: 400px; overflow: hidden; position: relative; } .related-content-tile a:hover { text-decoration: none; } .related-content-teaser { color:#fff; position: absolute; top: 0; left: 0; width: 100%; background: rgb(0,73,130) !important; transition-property: all; transition-duration: .5s; transition-timing-function: cubic-bezier(0, 1, 0.5, 1); height: 0; overflow: hidden; padding: 0; opacity: 0.95; font-size: 1.0em; -webkit-font-smoothing: antialiased; -moz-osx-font-smoothing: grayscale; font-family: 'Noto Serif',serif; font-size: 16px; font-weight: 400; line-height: 25.5px; } .related-content-teaser-content { padding: 20px; } .related-content-tile:hover { cursor: pointer; } .related-content-tile:hover .related-content-teaser { z-index: 1; height: 400px; } .related-content-tile p:first-child { display: none; } .related-content-tile h4 { padding: 0 10px 10px; font-family: 'Source Sans Pro',sans-serif; font-size: 19px; line-height: 22.5px; color:#444; } .related-content-meta, .related-content-tile a { color:#444; } .related-content-tile a:hover { color:#444; } @media only screen and (min-width: 769px) { .related-content-tile h4 { font-size:23px; line-height: 28.5px; letter-spacing: -0.5px; } } .related-content-meta { /*padding: 0 10px;*/ position: absolute; bottom: 10px; left: 0; border: rgb(212,212,212) !important; font-family: 'Noto Serif',serif; } p.related-content-meta { margin-bottom:0; font-size:15px; } .related-content-meta a { border: rgb(212,212,212) !important; } .related-content-tile-img { margin-bottom: 10px; width: 100%; background-position: center center; background-size: cover; height:75%; } @media (max-width: 375px) { .related-content-tile-img { height:60%; } } @media (min-width: 992px) { .related-content-tile-img { height:55%; } } @media (min-width: 1200px) { .related-content-tile-img { height:65%; } } @media (min-width: 1367px) { .related-content-tile-img { height:60%; } } .yarpp-related h3 { font-size: 28px!important; line-height: 31px; font-weight:400!important; } </style> <hr /><h3>DISCOVER: Related stories</h3><div class="row"><a rel="external" href="https://www.cshl.edu/making-ai-algorithms-show-their-work/"> <div class="col-md-4"><div class="related-content-tile"> <div class="related-content-tile-img" style="background-image:url(https://www.cshl.edu/wp-content/uploads/2021/05/Peter_Koo_2L6A2786-814x458.jpg)"></div><h4>Making AI algorithms show their work</h4><div class="related-content-teaser"><div class="related-content-teaser-content">AI machines are often better than humans at discerning patterns. 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Decades of quantitative genetics knowledge.   <strong>Read more »</strong></div></div><p class="related-content-meta">   <i class="fa fa-calendar-o"></i> June 21, 2024</p></div></div></a></div><hr/> </div> </main> </div> </div> </div> </div> </div> <footer id="colophon" class="site-footer" role="contentinfo"> <div class="container-fluid"> <section> <br/> </section> <div class="row"> <div class="col-lg-offset-1 col-lg-11 col-xs-12"> <div class="row"> <div class="col-lg-3 col-md-3 col-sm-3 col-xs-12 bottom-footer-column"> <h3 class="footer-contact-h3">Main Menu</h3> <ul id="footer-column-1" class="menu"><li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-29002"><a href="https://www.cshl.edu/about-us/">About</a></li> <li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-29003"><a href="https://www.cshl.edu/public-events/">Events</a></li> <li class="menu-item menu-item-type-post_type menu-item-object-page menu-item-29004"><a 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