
{"id":125510,"date":"2025-04-30T20:05:00","date_gmt":"2025-04-30T18:05:00","guid":{"rendered":"https:\/\/ibecbarcelona.eu\/?p=125510"},"modified":"2025-04-29T15:50:29","modified_gmt":"2025-04-29T13:50:29","slug":"explainable-ai-cracks-secret-language-of-sticky-proteins","status":"publish","type":"post","link":"https:\/\/ibecbarcelona.eu\/ca\/canya-la-ia-catalana-que-desxifra-el-llenguatge-secret-de-les-proteines-enganxoses","title":{"rendered":"CANYA, la IA catalana que desxifra el llenguatge secret de les prote\u00efnes &#8220;enganxoses&#8221;"},"content":{"rendered":"\n<p><strong>La nova IA aconsegueix predir quan i per qu\u00e8 t\u00e9 lloc l&#8217;agregaci\u00f3 de prote\u00efnes, un mecanisme vinculat a l&#8217;alzheimer i altres 50 malalties que afecten 500 milions de persones.<\/strong> <strong>Els resultats mostren un gran potencial per a la recerca en malalties neurodegeneratives i la millora de la producci\u00f3 de f\u00e0rmacs, reduint costos i augmentant l&#8217;efici\u00e8ncia.<\/strong> <strong>L&#8217;estudi, publicat a\u00a0<em>Science Advances<\/em>, \u00e9s fruit de la col\u00b7laboraci\u00f3 entre el Centre de Regulaci\u00f3 Gen\u00f2mica (CRG) i l&#8217;Institut de Bioenginyeria de Catalunya (IBEC).<\/strong><\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><img decoding=\"async\" width=\"1200\" height=\"675\" data-src=\"https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/FullSizeRender-1_low-edited.jpeg\" alt=\"\" class=\"wp-image-125499 lazyload\" data-srcset=\"https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/FullSizeRender-1_low-edited.jpeg 1200w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/FullSizeRender-1_low-edited-300x169.jpeg 300w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/FullSizeRender-1_low-edited-1024x576.jpeg 1024w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/FullSizeRender-1_low-edited-768x432.jpeg 768w\" data-sizes=\"(max-width: 1200px) 100vw, 1200px\" src=\"data:image\/svg+xml;base64,PHN2ZyB3aWR0aD0iMSIgaGVpZ2h0PSIxIiB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciPjwvc3ZnPg==\" style=\"--smush-placeholder-width: 1200px; --smush-placeholder-aspect-ratio: 1200\/675;\" \/><figcaption class=\"wp-element-caption\">D&#8217;esquerra a dreta: Ben Lehner (CRG), Mike Thompson (CRG) i Benedetta Bolognesi (IBEC)<\/figcaption><\/figure>\n\n\n\n<p>Una eina d&#8217;intel\u00b7lig\u00e8ncia artificial ha perm\u00e8s fer un important pas en la traducci\u00f3 del llenguatge que utilitzen les prote\u00efnes per dictar si formen agregats enganxosos, la pres\u00e8ncia dels quals es relaciona amb l&#8217;alzheimer i altres cinquanta tipus de malalties humanes. A difer\u00e8ncia dels t\u00edpics models d&#8217;IA de &#8220;caixa negra&#8221;, la nova eina, CANYA, es va dissenyar per poder explicar les seves decisions, revelant els patrons qu\u00edmics espec\u00edfics que impulsen o prevenen l&#8217;agregaci\u00f3 nociva de les prote\u00efnes.<a><\/a><\/p>\n\n\n\n<p>El descobriment, publicat a la revista <em>Science Advances<\/em>, ha estat possible gr\u00e0cies al conjunt m\u00e9s gran de dades sobre agregaci\u00f3 de prote\u00efnes creat fins ara. L&#8217;estudi ofereix nous coneixements sobre els mecanismes moleculars que causen l&#8217;agregaci\u00f3, que est\u00e0 relacionada amb malalties que afecten 500 milions de persones a tot el m\u00f3n.<\/p>\n\n\n\n<p>L&#8217;aglomeraci\u00f3 de prote\u00efnes, o agregaci\u00f3 amiloide, \u00e9s un perill per a la salut que altera la funci\u00f3 normal de les c\u00e8l\u00b7lules. Quan certes parts de les prote\u00efnes s&#8217;adhereixen entre si, aquestes es converteixen en masses denses i fibroses que tenen conseq\u00fc\u00e8ncies patol\u00f2giques.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p>L&#8217;agregaci\u00f3 de prote\u00efnes \u00e9s un gran mal de cap per a les companyies farmac\u00e8utiques. CANYA pot ajudar a guiar els esfor\u00e7os per dissenyar anticossos i enzims que tinguin menys probabilitats d&#8217;adherir-se i reduir els contratemps en el proc\u00e9s.<\/p>\n\n\n\n<p>Benedetta Bolognesi<\/p>\n<\/blockquote>\n\n\n\n<p>Si b\u00e9 l&#8217;estudi t\u00e9 algunes implicacions per accelerar els esfor\u00e7os en la recerca de malalties neurodegeneratives, el seu impacte m\u00e9s immediat ser\u00e0 en la biotecnologia. Molts f\u00e0rmacs s\u00f3n prote\u00efnes i, sovint, la seva funci\u00f3 es veu obstaculitzada per agregacions no desitjades.<\/p>\n\n\n\n<p>&#8220;L&#8217;agregaci\u00f3 de prote\u00efnes \u00e9s un gran mal de cap per a les companyies farmac\u00e8utiques&#8221;, afirma la Dra. <strong>Benedetta Bolognesi<\/strong>, coautora principal de l&#8217;estudi i l\u00edder de grup a l&#8217;Institut de Bioenginyeria de Catalunya (IBEC).<\/p>\n\n\n\n<p>&#8220;Si una prote\u00efna terap\u00e8utica comen\u00e7a a agregar-se, els lots de fabricaci\u00f3 poden fallar, cosa que costa temps i diners. CANYA pot ajudar a guiar els esfor\u00e7os per dissenyar anticossos i enzims que tinguin menys probabilitats d&#8217;adherir-se i reduir els contratemps en el proc\u00e9s&#8221;, afegeix.<a><\/a><\/p>\n\n\n\n<p>Les agregacions proteiques es formen utilitzant un llenguatge encara poc conegut. Les prote\u00efnes estan formades per vint tipus diferents d&#8217;amino\u00e0cids. En lloc de les habituals lletres A, C, G, T que componen el llenguatge de l&#8217;ADN, el llenguatge d&#8217;una prote\u00efna t\u00e9 vint lletres diferents, les combinacions de les quals formen &#8220;paraules&#8221; o &#8220;motius&#8221;.<\/p>\n\n\n\n<p>S&#8217;ha intentat durant molt de temps desxifrar quines combinacions de motius causen l&#8217;agregaci\u00f3 amiloide i quines altres permeten que les prote\u00efnes es pleguin sense errors. Les eines d&#8217;intel\u00b7lig\u00e8ncia artificial que tracten els amino\u00e0cids com l&#8217;alfabet d&#8217;un idioma misteri\u00f3s podrien ajudar a identificar les paraules o motius espec\u00edfics responsables, per\u00f2 la qualitat i el volum de les dades sobre l&#8217;agregaci\u00f3 de prote\u00efnes necess\u00e0ries per alimentar els models han estat hist\u00f2ricament escassos o s&#8217;han restringit a fragments de prote\u00efnes molt petits.<\/p>\n\n\n\n<p>L&#8217;estudi ha abordat aquest repte mitjan\u00e7ant la realitzaci\u00f3 d&#8217;experiments a gran escala. Els autors del treball van crear m\u00e9s de 100.000 fragments de prote\u00efnes completament aleatoris des de zero, cadascun de 20 amino\u00e0cids de llarg. La capacitat de cada fragment sint\u00e8tic per agregar-se es va provar en c\u00e8l\u00b7lules de llevat vives. Aix\u00ed, si un fragment en concret desencaden\u00e9s la formaci\u00f3 d&#8217;agregats, les c\u00e8l\u00b7lules de llevat creixerien d&#8217;una manera particular que pot ser mesurada per determinar la causa i l&#8217;efecte.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p>Hem creat fragments de prote\u00efnes aleatoris, incloses moltes versions que no es troben a la natura, proporcionant una gran quantitat de punts de dades per ajudar a comprendre les lleis m\u00e9s generals del comportament d&#8217;agregaci\u00f3<\/p>\n\n\n\n<p>Mike Thompson<\/p>\n<\/blockquote>\n\n\n\n<p>Al voltant d&#8217;un de cada cinc fragments de prote\u00efna (21.936\/100.000) va causar aglomeraci\u00f3, mentre que la resta no ho va fer. Si b\u00e9 estudis anteriors han pogut rastrejar un grapat de seq\u00fc\u00e8ncies, el nou conjunt de dades ha registrat un cat\u00e0leg molt m\u00e9s gran de les diferents variants de prote\u00efnes que poden causar l&#8217;agregaci\u00f3 amiloide.<\/p>\n\n\n\n<p>&#8220;Hem creat fragments de prote\u00efnes aleatoris, incloses moltes versions que no es troben a la natura. L&#8217;evoluci\u00f3 ha explorat nom\u00e9s una fracci\u00f3 de totes les seq\u00fc\u00e8ncies de prote\u00efna possibles, mentre que el nostre enfocament ens ajuda a endinsar-nos a una gal\u00e0xia molt m\u00e9s gran de possibilitats, proporcionant una gran quantitat de punts de dades per ajudar a comprendre les lleis m\u00e9s generals del comportament d&#8217;agregaci\u00f3&#8221;, explica el Dr. <strong>Mike Thompson<\/strong>, primer autor de l&#8217;estudi i investigador postdoctoral al Centre de Regulaci\u00f3 Gen\u00f2mica (CRG).<\/p>\n\n\n\n<p>La gran quantitat de dades generades a partir dels experiments es va utilitzar per entrenar CANYA. L&#8217;equip va decidir crear-la fent servir els principis de la &#8220;IA explicable&#8221;, fent que els seus processos de presa de decisions fossin transparents i comprensibles per als humans. Aix\u00f2 va significar sacrificar part del seu poder predictiu, que sol ser m\u00e9s gran a les IA de &#8220;caixa negra&#8221;. Malgrat aix\u00f2, CANYA va demostrar ser al voltant d&#8217;un 15% m\u00e9s precisa que els models existents.<\/p>\n\n\n\n<p>En concret, CANYA \u00e9s un model de convoluci\u00f3-atenci\u00f3, una eina h\u00edbrida que manlleva de dues \u00e0rees diferents de la IA. Els models de convoluci\u00f3, com els que s&#8217;utilitzen en el reconeixement d&#8217;imatges, escanegen les fotos tot cercant caracter\u00edstiques com una orella o un nas per identificar una cara. De manera equivalent, CANYA escaneja la cadena de prote\u00efnes per trobar caracter\u00edstiques significatives com motius o &#8220;paraules&#8221;.<\/p>\n\n\n\n<p>D&#8217;altra banda, les eines de traducci\u00f3 d&#8217;idiomes utilitzen els models d&#8217;IA per identificar frases clau en una oraci\u00f3 abans de decidir quina \u00e9s la millor traducci\u00f3. L&#8217;equip va incorporar aquesta t\u00e8cnica per ajudar CANYA a descobrir quins motius s\u00f3n els m\u00e9s importants a escala general de tota la prote\u00efna.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"alignright size-large is-resized\"><img decoding=\"async\" width=\"1024\" height=\"780\" data-src=\"https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/ab42-SHOW-merge_low-1024x780.jpg\" alt=\"\" class=\"wp-image-125502 lazyload\" style=\"--smush-placeholder-width: 1024px; --smush-placeholder-aspect-ratio: 1024\/780;width:300px\" data-srcset=\"https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/ab42-SHOW-merge_low-1024x780.jpg 1024w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/ab42-SHOW-merge_low-300x229.jpg 300w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/ab42-SHOW-merge_low-768x585.jpg 768w, https:\/\/ibecbarcelona.eu\/wp-content\/uploads\/2025\/04\/ab42-SHOW-merge_low.jpg 1200w\" data-sizes=\"(max-width: 1024px) 100vw, 1024px\" src=\"data:image\/svg+xml;base64,PHN2ZyB3aWR0aD0iMSIgaGVpZ2h0PSIxIiB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciPjwvc3ZnPg==\" \/><figcaption class=\"wp-element-caption\">Agregats amiloides a l&#8217;interior de c\u00e8l\u00b7lules marcades mitjan\u00e7ant t\u00e8cniques de fluoresc\u00e8ncia\/ <strong>Cr\u00e8dit<\/strong>: Benedetta Bolognesi (IBEC)\u00a0<\/figcaption><\/figure><\/div>\n\n\n<p>Junts, aquests dos enfocaments ajuden CANYA a veure de prop els motius locals i, alhora, a detectar la seva import\u00e0ncia a gran escala. Es pot fer servir aquesta informaci\u00f3 no nom\u00e9s per predir quins motius a la cadena de prote\u00efnes fomenten l&#8217;aglomeraci\u00f3, la bloquegen o provoquen un estadi intermedi, sin\u00f3 tamb\u00e9 per comprendre per qu\u00e8.<\/p>\n\n\n\n<p>Per exemple, CANYA va demostrar que les petites regions d&#8217;amino\u00e0cids repel\u00b7lents a l&#8217;aigua s\u00f3n m\u00e9s propenses a provocar aglomeraci\u00f3, mentre que alguns motius tenen un major impacte en l&#8217;aglomeraci\u00f3 si es troben cap a l&#8217;inici d&#8217;una seq\u00fc\u00e8ncia de prote\u00efnes en lloc de cap al final. Aquestes observacions s&#8217;alineen amb troballes pr\u00e8vies que s&#8217;han vist sota el microscopi en fibril\u00b7les amiloides conegudes.<\/p>\n\n\n\n<p>Per\u00f2 CANYA tamb\u00e9 va trobar noves regles que dirigeixen l&#8217;agregaci\u00f3 de prote\u00efnes. Per exemple, es pensava que certs components b\u00e0sics de les prote\u00efnes, els anomenats amino\u00e0cids carregats, eviten l&#8217;aglomeraci\u00f3. Per\u00f2 resulta que, en el context d&#8217;altres blocs de construcci\u00f3 espec\u00edfics, en realitat poden promoure l&#8217;aglomeraci\u00f3.<\/p>\n\n\n\n<p>En la seva forma actual, CANYA explica principalment l&#8217;agregaci\u00f3 de prote\u00efnes en termes de s\u00ed o no, \u00e9s a dir, funciona com un anomenat &#8220;classificador&#8221;. Com a treball futur, l&#8217;equip vol refinar el sistema perqu\u00e8 pugui predir i comparar les velocitats d&#8217;agregaci\u00f3 en lloc de nom\u00e9s la probabilitat d&#8217;agregaci\u00f3. Aix\u00f2 podria ajudar a predir quines variants de prote\u00efnes formen agregats r\u00e0pidament i quines ho fan m\u00e9s lentament, un factor vital en les malalties neurodegeneratives en qu\u00e8 el moment de la formaci\u00f3 d&#8217;amiloide \u00e9s tan important com el fet mateix que passi.<\/p>\n\n\n\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p>Aquest projecte \u00e9s un gran exemple de com la combinaci\u00f3 de la generaci\u00f3 de dades a gran escala amb la IA pot accelerar la recerca. Tamb\u00e9 es tracta d&#8217;un m\u00e8tode molt rendible per generar dades.<\/p>\n\n\n\n<p>Ben Lehner<\/p>\n<\/blockquote>\n\n\n\n<p>&#8220;Hi ha 1.024 quintilions de formes de crear un fragment de prote\u00efna de 20 amino\u00e0cids de llarg. Fins ara, hem entrenat una IA amb nom\u00e9s 100.000 fragments. Volem millorar el proc\u00e9s creant m\u00e9s fragments i m\u00e9s grans. Tot i que aquest \u00e9s nom\u00e9s el primer pas, el nostre treball mostra que \u00e9s possible desxifrar el llenguatge de l&#8217;agregaci\u00f3 de prote\u00efnes. Aix\u00f2 \u00e9s incre\u00efblement important per a la nostra comprensi\u00f3 de les malalties humanes, per\u00f2 tamb\u00e9 per guiar els esfor\u00e7os de la biologia sint\u00e8tica&#8221;, conclou la Dra. Bolognesi.<\/p>\n\n\n\n<p>&#8220;Aquest projecte \u00e9s un gran exemple de com la combinaci\u00f3 de la generaci\u00f3 de dades a gran escala amb la IA pot accelerar la recerca. Tamb\u00e9 es tracta d&#8217;un m\u00e8tode molt rendible per generar dades&#8221;, diu el professor de recerca ICREA <strong>Ben Lehner<\/strong>, coautor principal de l&#8217;estudi i cap de grup al Centre de Regulaci\u00f3 Gen\u00f2mica (CRG) i l&#8217;Institut Wellcome Sanger.<\/p>\n\n\n\n<p>&#8220;Usant la s\u00edntesi i seq\u00fcenciaci\u00f3 d&#8217;ADN, podem realitzar centenars de milers d&#8217;experiments en un sol tub, generant les dades que necessitem per entrenar models d&#8217;IA. Aquest \u00e9s un enfocament que estem aplicant a molts problemes dif\u00edcils de la biologia, amb l&#8217;objectiu que aquesta sigui predictible i programable&#8221;, afegeix Dr. Lehner.<\/p>\n\n\n\n<p>L&#8217;estudi \u00e9s fruit de la col\u00b7laboraci\u00f3 entre el laboratori del professor de recerca ICREA Ben Lehner al Centre de Regulaci\u00f3 Gen\u00f2mica (CRG) i el laboratori de Benedetta Bolognesi a l&#8217;Institut de Bioenginyeria de Catalunya (IBEC). Equips del Laboratori Cold Spring Harbor (CSHL) i l&#8217;Institut Wellcome Sanger tamb\u00e9 van col\u00b7laborar en l&#8217;estudi.&nbsp; El treball ha rebut finan\u00e7ament de la Fundaci\u00f3 de Recerca &#8220;la Caixa&#8221;, el Consell Europeu de Recerca i el Ministeri de Ci\u00e8ncia i Innovaci\u00f3.<\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<p><strong>Reference article<\/strong><\/p>\n\n\n\n<p>Mike Thompson, Mariano Mart\u00edn, Trinidad Sanmart\u00edn Olmo, Chandana Rajesh, Peter K. Koo, Benedetta Bolognesi, Ben Lehner. <strong>Massive experimental quantification allows interpretable deep learning of protein aggregation. <\/strong><em>Science Advances <\/em>(2025). DOI: <a href=\"https:\/\/doi.org\/10.1126\/sciadv.adt5111\" target=\"_blank\" rel=\"noreferrer noopener\">10.1126\/sciadv.adt5111<\/a><\/p>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n","protected":false},"excerpt":{"rendered":"<p>La nova IA aconsegueix predir quan i per qu\u00e8 t\u00e9 lloc l&#8217;agregaci\u00f3 de prote\u00efnes, un mecanisme vinculat a l&#8217;alzheimer i altres 50 malalties que afecten 500 milions de persones. Els resultats mostren un gran potencial per a la recerca en malalties neurodegeneratives i la millora de la producci\u00f3 de f\u00e0rmacs, reduint costos i augmentant l&#8217;efici\u00e8ncia. L&#8217;estudi, publicat a\u00a0Science Advances, \u00e9s fruit de la col\u00b7laboraci\u00f3 entre el Centre de Regulaci\u00f3 Gen\u00f2mica (CRG) i l&#8217;Institut de Bioenginyeria de Catalunya (IBEC).<\/p>\n","protected":false},"author":37,"featured_media":125497,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[96],"tags":[1627,2152,1107,1776],"post_formats":[],"class_list":["post-125510","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-noticies-de-recerca","tag-alzheimer-ca-2","tag-artificial-intelligence-ca","tag-benedetta-bolognesi-ca","tag-protein-phase-transitions-in-health-and-disease-ca"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>CANYA, la IA catalana que desxifra el llenguatge secret de les prote\u00efnes &quot;enganxoses&quot; - Institute for Bioengineering of Catalonia<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibecbarcelona.eu\/ca\/canya-la-ia-catalana-que-desxifra-el-llenguatge-secret-de-les-proteines-enganxoses\/\" \/>\n<meta property=\"og:locale\" content=\"ca_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"CANYA, la IA catalana que desxifra el llenguatge secret de les prote\u00efnes &quot;enganxoses&quot; - Institute for Bioengineering of Catalonia\" \/>\n<meta property=\"og:description\" content=\"La nova IA aconsegueix predir quan i per qu\u00e8 t\u00e9 lloc l&#039;agregaci\u00f3 de prote\u00efnes, un mecanisme vinculat a l&#039;alzheimer i altres 50 malalties que afecten 500 milions de persones. Els resultats mostren un gran potencial per a la recerca en malalties neurodegeneratives i la millora de la producci\u00f3 de f\u00e0rmacs, reduint costos i augmentant l&#039;efici\u00e8ncia. 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