Towards a proteome-scale map of the human protein–protein interaction network

<!DOCTYPE html> <html lang="en" class="grade-c"> <head> <title>Towards a proteome-scale map of the human protein–protein interaction network | Nature</title> <link rel="alternate" type="application/rss+xml" href="https://www.nature.com/nature.rss"/> <script id="save-data-connection-testing"> function hasConnection() { return navigator.connection || navigator.mozConnection || navigator.webkitConnection || navigator.msConnection; } function createLink(src) { var preloadLink = document.createElement("link"); preloadLink.rel = "preload"; preloadLink.href = src; preloadLink.as = "font"; preloadLink.type = "font/woff2"; preloadLink.crossOrigin = ""; document.head.insertBefore(preloadLink, document.head.firstChild); } var connectionDetail = { saveDataEnabled: false, slowConnection: false }; var connection = hasConnection(); if (connection) { connectionDetail.saveDataEnabled = connection.saveData; if (/\slow-2g|2g/.test(connection.effectiveType)) { connectionDetail.slowConnection = true; } } if (!(connectionDetail.saveDataEnabled || connectionDetail.slowConnection)) { createLink("/static/fonts/HardingText-Regular-Web-cecd90984f.woff2"); } else { document.documentElement.classList.add('save-data'); } </script> <link rel="preconnect" href="https://cmp.nature.com" crossorigin> <meta http-equiv="X-UA-Compatible" content="IE=edge"> <meta name="applicable-device" content="pc,mobile"> <meta name="viewport" content="width=device-width,initial-scale=1.0,maximum-scale=5,user-scalable=yes"> <meta name="360-site-verification" content="5a2dc4ab3fcb9b0393241ffbbb490480" /> <script data-test="dataLayer"> window.dataLayer = [{"content":{"category":{"contentType":"letter","legacy":{"webtrendsPrimaryArticleType":"research","webtrendsSubjectTerms":null,"webtrendsContentCategory":null,"webtrendsContentCollection":null,"webtrendsContentGroup":"Nature","webtrendsContentGroupType":null,"webtrendsContentSubGroup":"Letter","status":null}},"article":{"doi":"10.1038/nature04209"},"attributes":{"cms":null,"deliveryPlatform":"oscar","copyright":{"open":false,"legacy":{"webtrendsLicenceType":null}}},"contentInfo":{"authors":["Jean-François Rual","Kavitha Venkatesan","Tong Hao","Tomoko Hirozane-Kishikawa","Amélie Dricot","Ning Li","Gabriel F. 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Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties8,9, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein–protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of ∼8,100 currently available Gateway-cloned open reading frames and detected ∼2,800 interactions. This data set, called CCSB-HI1, has a verification rate of ∼78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by ∼70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. 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itemscope itemtype="https://schema.org/ListItem"> <span itemprop="name">article</span><meta itemprop="position" content="3"></li> </ol> </div> </nav> </div> <div class="u-container u-mt-32 u-mb-32 u-clearfix" id="content" data-component="article-container" data-container-type="article"> <main class="c-article-main-column u-float-left js-main-column" data-track-component="article body"> <article lang="en"> <div class="c-article-header"> <header> <ul class="c-article-identifiers" data-test="article-identifier"> <li class="c-article-identifiers__item" data-test="article-category">Letter</li> <li class="c-article-identifiers__item">Published: <time datetime="2005-09-28">28 September 2005</time></li> </ul> <h1 class="c-article-title" data-test="article-title" data-article-title="">Towards a proteome-scale map of the human protein–protein interaction network</h1> <ul class="c-article-author-list c-article-author-list--long" data-test="authors-list" data-component-authors-activator="authors-list"><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Jean_Fran_ois-Rual-Aff1" data-author-popup="auth-Jean_Fran_ois-Rual-Aff1" data-author-search="Rual, Jean-François">Jean-François Rual</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup><sup class="u-js-hide"> <a href="#na1">na1</a></sup>, </li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Kavitha-Venkatesan-Aff1" data-author-popup="auth-Kavitha-Venkatesan-Aff1" data-author-search="Venkatesan, Kavitha">Kavitha Venkatesan</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup><sup class="u-js-hide"> <a href="#na1">na1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Tong-Hao-Aff1" data-author-popup="auth-Tong-Hao-Aff1" data-author-search="Hao, Tong">Tong Hao</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Tomoko-Hirozane_Kishikawa-Aff1" data-author-popup="auth-Tomoko-Hirozane_Kishikawa-Aff1" data-author-search="Hirozane-Kishikawa, Tomoko">Tomoko Hirozane-Kishikawa</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Am_lie-Dricot-Aff1" data-author-popup="auth-Am_lie-Dricot-Aff1" data-author-search="Dricot, Amélie">Amélie Dricot</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Ning-Li-Aff1" data-author-popup="auth-Ning-Li-Aff1" data-author-search="Li, Ning">Ning Li</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Gabriel_F_-Berriz-Aff2" data-author-popup="auth-Gabriel_F_-Berriz-Aff2" data-author-search="Berriz, Gabriel F.">Gabriel F. Berriz</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Francis_D_-Gibbons-Aff2" data-author-popup="auth-Francis_D_-Gibbons-Aff2" data-author-search="Gibbons, Francis D.">Francis D. Gibbons</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Matija-Dreze-Aff1-Aff3" data-author-popup="auth-Matija-Dreze-Aff1-Aff3" data-author-search="Dreze, Matija">Matija Dreze</a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff3">3</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Nono-Ayivi_Guedehoussou-Aff1" data-author-popup="auth-Nono-Ayivi_Guedehoussou-Aff1" data-author-search="Ayivi-Guedehoussou, Nono">Nono Ayivi-Guedehoussou</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Niels-Klitgord-Aff1" data-author-popup="auth-Niels-Klitgord-Aff1" data-author-search="Klitgord, Niels">Niels Klitgord</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Christophe-Simon-Aff1" data-author-popup="auth-Christophe-Simon-Aff1" data-author-search="Simon, Christophe">Christophe Simon</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Mike-Boxem-Aff1" data-author-popup="auth-Mike-Boxem-Aff1" data-author-search="Boxem, Mike">Mike Boxem</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Stuart-Milstein-Aff1" data-author-popup="auth-Stuart-Milstein-Aff1" data-author-search="Milstein, Stuart">Stuart Milstein</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Jennifer-Rosenberg-Aff1" data-author-popup="auth-Jennifer-Rosenberg-Aff1" data-author-search="Rosenberg, Jennifer">Jennifer Rosenberg</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Debra_S_-Goldberg-Aff2" data-author-popup="auth-Debra_S_-Goldberg-Aff2" data-author-search="Goldberg, Debra S.">Debra S. Goldberg</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Lan_V_-Zhang-Aff2" data-author-popup="auth-Lan_V_-Zhang-Aff2" data-author-search="Zhang, Lan V.">Lan V. Zhang</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Sharyl_L_-Wong-Aff2" data-author-popup="auth-Sharyl_L_-Wong-Aff2" data-author-search="Wong, Sharyl L.">Sharyl L. Wong</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Giovanni-Franklin-Aff2" data-author-popup="auth-Giovanni-Franklin-Aff2" data-author-search="Franklin, Giovanni">Giovanni Franklin</a><sup class="u-js-hide"><a href="#Aff2">2</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Siming-Li-Aff1-Aff7" data-author-popup="auth-Siming-Li-Aff1-Aff7" data-author-search="Li, Siming">Siming Li</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup><sup class="u-js-hide"> <a href="#nAff7">nAff7</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Joanna_S_-Albala-Aff1-Aff8" data-author-popup="auth-Joanna_S_-Albala-Aff1-Aff8" data-author-search="Albala, Joanna S.">Joanna S. Albala</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup><sup class="u-js-hide"> <a href="#nAff8">nAff8</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Janghoo-Lim-Aff4" data-author-popup="auth-Janghoo-Lim-Aff4" data-author-search="Lim, Janghoo">Janghoo Lim</a><sup class="u-js-hide"><a href="#Aff4">4</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Carlene-Fraughton-Aff1" data-author-popup="auth-Carlene-Fraughton-Aff1" data-author-search="Fraughton, Carlene">Carlene Fraughton</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Estelle-Llamosas-Aff1" data-author-popup="auth-Estelle-Llamosas-Aff1" data-author-search="Llamosas, Estelle">Estelle Llamosas</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Sebiha-Cevik-Aff1" data-author-popup="auth-Sebiha-Cevik-Aff1" data-author-search="Cevik, Sebiha">Sebiha Cevik</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Camille-Bex-Aff1" data-author-popup="auth-Camille-Bex-Aff1" data-author-search="Bex, Camille">Camille Bex</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Philippe-Lamesch-Aff1-Aff3" data-author-popup="auth-Philippe-Lamesch-Aff1-Aff3" data-author-search="Lamesch, Philippe">Philippe Lamesch</a><sup class="u-js-hide"><a href="#Aff1">1</a>,<a href="#Aff3">3</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Robert_S_-Sikorski-Aff5" data-author-popup="auth-Robert_S_-Sikorski-Aff5" data-author-search="Sikorski, Robert S.">Robert S. Sikorski</a><sup class="u-js-hide"><a href="#Aff5">5</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Jean-Vandenhaute-Aff3" data-author-popup="auth-Jean-Vandenhaute-Aff3" data-author-search="Vandenhaute, Jean">Jean Vandenhaute</a><sup class="u-js-hide"><a href="#Aff3">3</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Huda_Y_-Zoghbi-Aff4" data-author-popup="auth-Huda_Y_-Zoghbi-Aff4" data-author-search="Zoghbi, Huda Y.">Huda Y. Zoghbi</a><sup class="u-js-hide"><a href="#Aff4">4</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Alex-Smolyar-Aff1" data-author-popup="auth-Alex-Smolyar-Aff1" data-author-search="Smolyar, Alex">Alex Smolyar</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Stephanie-Bosak-Aff6" data-author-popup="auth-Stephanie-Bosak-Aff6" data-author-search="Bosak, Stephanie">Stephanie Bosak</a><sup class="u-js-hide"><a href="#Aff6">6</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Reynaldo-Sequerra-Aff6" data-author-popup="auth-Reynaldo-Sequerra-Aff6" data-author-search="Sequerra, Reynaldo">Reynaldo Sequerra</a><sup class="u-js-hide"><a href="#Aff6">6</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Lynn-Doucette_Stamm-Aff6" data-author-popup="auth-Lynn-Doucette_Stamm-Aff6" data-author-search="Doucette-Stamm, Lynn">Lynn Doucette-Stamm</a><sup class="u-js-hide"><a href="#Aff6">6</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Michael_E_-Cusick-Aff1" data-author-popup="auth-Michael_E_-Cusick-Aff1" data-author-search="Cusick, Michael E.">Michael E. Cusick</a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-David_E_-Hill-Aff1" data-author-popup="auth-David_E_-Hill-Aff1" data-author-search="Hill, David E." data-corresp-id="c1">David E. Hill<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a></sup>, </li><li class="c-article-author-list__item c-article-author-list__item--hide c-article-author-list__item--hide-small-screen"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Frederick_P_-Roth-Aff2" data-author-popup="auth-Frederick_P_-Roth-Aff2" data-author-search="Roth, Frederick P." data-corresp-id="c2">Frederick P. Roth<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff2">2</a></sup> & </li><li class="c-article-author-list__show-more" aria-label="Show all 38 authors for this article" title="Show all 38 authors for this article">…</li><li class="c-article-author-list__item"><a data-test="author-name" data-track="click" data-track-action="open author" data-track-label="link" href="#auth-Marc-Vidal-Aff1" data-author-popup="auth-Marc-Vidal-Aff1" data-author-search="Vidal, Marc" data-corresp-id="c3">Marc Vidal<svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-mail-medium"></use></svg></a><sup class="u-js-hide"><a href="#Aff1">1</a></sup> </li></ul><button aria-expanded="false" class="c-article-author-list__button"><svg width="16" height="16" focusable="false" role="img" aria-hidden="true" class="u-icon"><use xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="#icon-eds-i-chevron-down-medium"></use></svg><span>Show authors</span></button> <p class="c-article-info-details" data-container-section="info"> <a data-test="journal-link" href="/" data-track="click" data-track-action="journal homepage" data-track-category="article body" data-track-label="link"><i data-test="journal-title">Nature</i></a> <b data-test="journal-volume"><span class="u-visually-hidden">volume</span> 437</b>, <span class="u-visually-hidden">pages </span>1173–1178 (<span data-test="article-publication-year">2005</span>)<a href="#citeas" class="c-article-info-details__cite-as u-hide-print" data-track="click" data-track-action="cite this article" data-track-label="link">Cite this article</a> </p> <div class="c-article-metrics-bar__wrapper u-clear-both"> <ul class="c-article-metrics-bar u-list-reset"> <li class=" c-article-metrics-bar__item" data-test="access-count"> <p class="c-article-metrics-bar__count">33k <span class="c-article-metrics-bar__label">Accesses</span></p> </li> <li class="c-article-metrics-bar__item" data-test="citation-count"> <p class="c-article-metrics-bar__count">2206 <span class="c-article-metrics-bar__label">Citations</span></p> </li> <li class="c-article-metrics-bar__item" data-test="altmetric-score"> <p class="c-article-metrics-bar__count">48 <span class="c-article-metrics-bar__label">Altmetric</span></p> </li> <li class="c-article-metrics-bar__item"> <p class="c-article-metrics-bar__details"><a href="/articles/nature04209/metrics" data-track="click" data-track-action="view metrics" data-track-label="link" rel="nofollow">Metrics <span class="u-visually-hidden">details</span></a></p> </li> </ul> </div> </header> </div> <div class="c-article-body"> <section aria-labelledby="Abs1" data-title="Abstract" lang="en"><div class="c-article-section" id="Abs1-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Abs1">Abstract</h2><div class="c-article-section__content" id="Abs1-content"><p>Systematic mapping of protein–protein interactions, or ‘interactome’ mapping, was initiated in model organisms, starting with defined biological processes<sup><a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 1" title="Fromont-Racine, M., Rain, J. C. & Legrain, P. Toward a functional analysis of the yeast genome through exhaustive two-hybrid screens. Nature Genet. 16, 277–282 (1997)" href="/articles/nature04209#ref-CR1" id="ref-link-section-d238038235e805">1</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 2" title="Walhout, A. J. et al. Protein interaction mapping in C. elegans using proteins involved in vulval development. Science 287, 116–122 (2000)" href="/articles/nature04209#ref-CR2" id="ref-link-section-d238038235e808">2</a></sup> and then expanding to the scale of the proteome<sup><a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 3" title="Uetz, P. et al. A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627 (2000)" href="/articles/nature04209#ref-CR3" id="ref-link-section-d238038235e812">3</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 4" title="Ito, T. et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc. Natl Acad. Sci. USA 98, 4569–4574 (2001)" href="/articles/nature04209#ref-CR4" id="ref-link-section-d238038235e815">4</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 5" title="Reboul, J. et al. C. elegans ORFeome version 1.1: experimental verification of the genome annotation and resource for proteome-scale protein expression. Nature Genet. 34, 35–41 (2003)" href="/articles/nature04209#ref-CR5" id="ref-link-section-d238038235e818">5</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 6" title="Giot, L. et al. A protein interaction map of Drosophila melanogaster. Science 302, 1727–1736 (2003)" href="/articles/nature04209#ref-CR6" id="ref-link-section-d238038235e821">6</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 7" title="Li, S. et al. A map of the interactome network of the metazoan C. elegans. Science 303, 540–543 (2004)" href="/articles/nature04209#ref-CR7" id="ref-link-section-d238038235e824">7</a></sup>. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties<sup><a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 8" title="Jeong, H., Mason, S. P., Barabasi, A. L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41–42 (2001)" href="/articles/nature04209#ref-CR8" id="ref-link-section-d238038235e828">8</a>,<a data-track="click" data-track-action="reference anchor" data-track-label="link" data-test="citation-ref" aria-label="Reference 9" title="Han, J. D. et al. Evidence for dynamically organized modularity in the yeast protein–protein interaction network. Nature 430, 88–93 (2004)" href="/articles/nature04209#ref-CR9" id="ref-link-section-d238038235e831">9</a></sup>, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein–protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of <span class="stix">∼</span>8,100 currently available Gateway-cloned open reading frames and detected <span class="stix">∼</span>2,800 interactions. This data set, called CCSB-HI1, has a verification rate of <span class="stix">∼</span>78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by <span class="stix">∼</span>70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.</p></div></div></section> <noscript> <div class="c-nature-box c-nature-box--side " data-component="entitlement-box"> <div class="js-access-button"> <a href="https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fnature04209" class="c-article__button" data-test="ra21"> <svg class="u-icon" width="18" height="18" aria-hidden="true" focusable="false"><use href="#icon-institution"></use></svg> <span class="c-article__button-text">Access through your institution</span> </a> </div> <div class="js-buy-button"> <a href="#access-options" class="c-article__button c-article__button--inverted" data-test="ra21"> <span>Buy or subscribe</span> </a> </div> </div> </noscript> <div class="js-context-bar-sticky-point-mobile" data-track-context="article body"> </div> <div class="c-article-access-provider u-mb-32 u-mt-0"> <p class="c-article-access-provider__text 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We thank members of the Vidal laboratory and the participants of the ORFeome Meeting for discussions; the sequencing staff at Agencourt Biosciences for technical assistance; E. Smith for his help with the figures; C. McCowan, A. Bird, T. Clingingsmith and C. You for administrative assistance; and E. Benz, S. Korsmeyer, D. Livingston, P. McCue, J. Song, B. Rollins and the DFCI Strategic Planning Initiative for support. Our human interactome project is supported by the DFCI High-Tech Fund (S. Korsmeyer), an Ellison Foundation grant awarded to M.V., an NIH/NCI grant awarded to S. Korsmeyer, S. Orkin, G. Gilliland and M.V., an ‘interactome mapping’ grant from NIH/NHGRI and NIH/NIGMS awarded to F.P.R. and M.V., and a W.M. Keck Foundation grant awarded to E. Benz, J. Marto, F.P.R. and M.V. Other support includes Taplin Funds for Discovery (F.P.R., F.D.G. and G.F.B), a 2003 NSF Fellowship (D.S.G) and funding from the Fonds National de la Recherche Scientifique, Belgium (M.D.). Author Contributions Experiments and data analyses were coordinated by J.F.R., T.H. and K.V. High-throughput ORF cloning and yeast two-hybrid screens were performed by J.F.R., T.H.K., A.D., N.L., N.A.G., J.R. and J.L. J.F.R developed the high-throughput yeast two-hybrid strategy. Computational analyses were performed by T.H., K.V., G.F.B., F.D.G., N.K., P.L., D.S.G., L.V.Z., S.L.W. and G.F. Co-affinity purification experiments were performed by M.D., C.S., J.F.R., S.M., M.B., S.L. and J.S.A. C.F., E.L., S.C. and C.B. provided laboratory support. R.S.S., J.V., H.Y.Z., A.S. and M.E.C. helped with the overall interpretation of the data. DNA sequencing was performed by S.B., R.S. and L.D.S. The manuscript was written by J.F.R., K.V., M.E.C., D.E.H., F.P.R. and M.V. The project was conceived by M.V. and co-directed by D.E.H., F.P.R. and M.V.</p></div></div></section><section aria-labelledby="author-information" data-title="Author information"><div class="c-article-section" id="author-information-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="author-information">Author information</h2><div class="c-article-section__content" id="author-information-content"><span class="c-article-author-information__subtitle u-visually-hidden" id="author-notes">Author notes</span><ol class="c-article-author-information__list"><li class="c-article-author-information__item" id="nAff7"><p class="c-article-author-information__authors-list">Siming Li</p><p class="js-present-address">Present address: ArQule, Inc., 19 Presidential Way, Woburn, Massachusetts, 01081, USA</p></li><li class="c-article-author-information__item" id="nAff8"><p class="c-article-author-information__authors-list">Joanna S. Albala</p><p class="js-present-address">Present address: Departments of Cancer Biology, and Otolaryngology, Head and Neck Surgery, University of California Davis, 2521 Stockton Blvd, Suite 7200, Sacramento, California, 95817, USA</p></li><li class="c-article-author-information__item" id="na1"><p>Jean-François Rual and Kavitha Venkatesan: *These authors contributed equally to this work</p></li></ol><h3 class="c-article__sub-heading" id="affiliations">Authors and Affiliations</h3><ol class="c-article-author-affiliation__list"><li id="Aff1"><p class="c-article-author-affiliation__address">Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, 44 Binney Street, Massachusetts, 02115, Boston, USA</p><p class="c-article-author-affiliation__authors-list">Jean-François Rual, Kavitha Venkatesan, Tong Hao, Tomoko Hirozane-Kishikawa, Amélie Dricot, Ning Li, Matija Dreze, Nono Ayivi-Guedehoussou, Niels Klitgord, Christophe Simon, Mike Boxem, Stuart Milstein, Jennifer Rosenberg, Siming Li, Joanna S. Albala, Carlene Fraughton, Estelle Llamosas, Sebiha Cevik, Camille Bex, Philippe Lamesch, Alex Smolyar, Michael E. Cusick, David E. Hill & Marc Vidal</p></li><li id="Aff2"><p class="c-article-author-affiliation__address">Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Ave, Massachusetts, 02115, Boston, USA</p><p class="c-article-author-affiliation__authors-list">Gabriel F. Berriz, Francis D. Gibbons, Debra S. Goldberg, Lan V. Zhang, Sharyl L. Wong, Giovanni Franklin & Frederick P. Roth</p></li><li id="Aff3"><p class="c-article-author-affiliation__address">Unité de Recherche en Biologie Moléculaire, Facultés Notre-Dame de la Paix, 61 Rue de Bruxelles, 5000, Namur, Belgium</p><p class="c-article-author-affiliation__authors-list">Matija Dreze, Philippe Lamesch & Jean Vandenhaute</p></li><li id="Aff4"><p class="c-article-author-affiliation__address">Howard Hughes Medical Institute, and Departments of Pediatrics, Neurology, Neuroscience, and Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Texas, 77030, Houston, USA</p><p class="c-article-author-affiliation__authors-list">Janghoo Lim & Huda Y. Zoghbi</p></li><li id="Aff5"><p class="c-article-author-affiliation__address">Arcbay, Inc., 6 Whittier Place, Suite 7J, Massachusetts, 01915, Boston, USA</p><p class="c-article-author-affiliation__authors-list">Robert S. Sikorski</p></li><li id="Aff6"><p class="c-article-author-affiliation__address">Agencourt Bioscience Corporation, 500 Cummings Center, Suite 2450, Massachusetts, 01915, Beverly, USA</p><p class="c-article-author-affiliation__authors-list">Stephanie Bosak, Reynaldo Sequerra & Lynn Doucette-Stamm</p></li></ol><div class="u-js-hide u-hide-print" data-test="author-info"><span class="c-article__sub-heading">Authors</span><ol class="c-article-authors-search u-list-reset"><li id="auth-Jean_Fran_ois-Rual-Aff1"><span class="c-article-authors-search__title u-h3 js-search-name">Jean-François Rual</span><div class="c-article-authors-search__list"><div class="c-article-authors-search__item c-article-authors-search__list-item--left"><a href="/search?author=Jean-Fran%C3%A7ois%20Rual" class="c-article-button" data-track="click" data-track-action="author link - publication" data-track-label="link" rel="nofollow">View author publications</a></div><div class="c-article-authors-search__item c-article-authors-search__list-item--right"><p class="search-in-title-js c-article-authors-search__text">You can also search for this author in <span class="c-article-identifiers"><a class="c-article-identifiers__item" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=search&term=Jean-Fran%C3%A7ois%20Rual" data-track="click" data-track-action="author link - 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Hill</a>, <a id="corresp-c2" href="mailto:fritz_roth@hms.harvard.edu">Frederick P. Roth</a> or <a id="corresp-c3" href="mailto:marc_vidal@dfci.harvard.edu">Marc Vidal</a>.</p></div></div></section><section data-title="Ethics declarations"><div class="c-article-section" id="ethics-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="ethics">Ethics declarations</h2><div class="c-article-section__content" id="ethics-content"> <h3 class="c-article__sub-heading">Competing interests</h3> <p>Reprints and permissions information is available at <a href="http://www.npg.nature.com/reprintsandpermissions">npg.nature.com/reprintsandpermissions</a>. The authors declare no competing financial interests.</p> </div></div></section><section data-title="Supplementary information"><div class="c-article-section" id="Sec3-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="Sec3">Supplementary information</h2><div class="c-article-section__content" id="Sec3-content"><div data-test="supplementary-info"><div id="figshareContainer" class="c-article-figshare-container" data-test="figshare-container"></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM1"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary data" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM1_ESM.doc" data-supp-info-image="">Supplementary Data</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>This file contains expanded information regarding various concepts discussed in the main paper, plus a Methods section. In addition, this file has a Supplementary Methods section and legends for the Supplementary Figures and Tables. (DOC 518 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM2"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s1a" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM2_ESM.pdf" data-supp-info-image="">Supplementary Figure S1a</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Filtering and quality assessment of Y2H interactions. (PDF 451 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM3"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s1b" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM3_ESM.pdf" data-supp-info-image="">Supplementary Figure S1b</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Filtering and quality assessment of Y2H interactions. (PDF 33623 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM4"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s1c" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM4_ESM.pdf" data-supp-info-image="">Supplementary Figure S1c</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Filtering and quality assessment of Y2H interactions. (PDF 3236 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM5"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s2" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM5_ESM.pdf" data-supp-info-image="">Supplementary Figure S2</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Bias in network neighborhoods for either CCSB-HI1 or LCI interactions. (PDF 225 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM6"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s3" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM6_ESM.pdf" data-supp-info-image="">Supplementary Figure S3</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Occurrence of CCSB-HI1-associated, LCI-associated associated gene pairs in Pubmed or Google Scholar searches. (PDF 200 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM7"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s4a" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM7_ESM.pdf" data-supp-info-image="">Supplementary Figure S4a </a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Correlation of interaction data with other gene- or protein-pair characteristics. (PDF 1646 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM8"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s4b" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM8_ESM.pdf" data-supp-info-image="">Supplementary Figure S4b</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Correlation of interaction data with other gene- or protein-pair characteristics. (PDF 233 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM9"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s5a" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM9_ESM.pdf" data-supp-info-image="">Supplementary Figure S5a </a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Network analyses of CCSB-HI1. (PDF 181 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM10"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s5b" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM10_ESM.pdf" data-supp-info-image="">Supplementary Figure S5b</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Network analyses of CCSB-HI1. (PDF 182 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM11"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s5c" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM11_ESM.pdf" data-supp-info-image="">Supplementary Figure S5c</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Network analyses of CCSB-HI1. (PDF 247 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM12"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s5d" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM12_ESM.pdf" data-supp-info-image="">Supplementary Figure S5d</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Network analyses of CCSB-HI1. (PDF 108 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM13"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s6a" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM13_ESM.pdf" data-supp-info-image="">Supplementary Figure S6a</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Sub-networks of putative biological modules. (PDF 476 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM14"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s6b" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM14_ESM.pdf" data-supp-info-image="">Supplementary Figure S6b</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Sub-networks of putative biological modules. (PDF 262 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM15"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary figure s6c" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM15_ESM.pdf" data-supp-info-image="">Supplementary Figure S6c</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Sub-networks of putative biological modules. (PDF 191 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM16"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s1" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM16_ESM.xls" data-supp-info-image="">Supplementary Table S1</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>List of all human ORFs in Space-I that were tested for Y2H interactions. (XLS 226 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM17"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s2" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM17_ESM.xls" data-supp-info-image="">Supplementary Table S2</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>List of CCSB-HI1 and LCI binary interactions along with annotation. (XLS 254 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM18"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s3" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM18_ESM.xls" data-supp-info-image="">Supplementary Table S3</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>List of CCSB-HI1 and LCI interactions that were tested in co-AP experiments. (XLS 6 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM19"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s4" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM19_ESM.xls" data-supp-info-image="">Supplementary Table S4</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>List of over-represented and under-represented Pfam-A domains in CCSB-HI1 and LCI data sets. (XLS 23 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM20"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s5" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM20_ESM.xls" data-supp-info-image="">Supplementary Table S5</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Analysis of overlap between CCSB-HI1 or LCI-interacting protein-pairs with other shared gene- or protein-pair characteristics. (XLS 43 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM21"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s6" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM21_ESM.xls" data-supp-info-image="">Supplementary Table S6</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Statistics of CCSB-HI1interactions between proteins in different evolutionary classes. (XLS 20 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM22"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s7" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM22_ESM.xls" data-supp-info-image="">Supplementary Table S7</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>List of 172 MCODE-generated clusters from the CCSB-HI1 network and the combined CCSB-HI1/LCI and CCSB-HI1/LC networks. (XLS 197 kb)</p></div></div><div class="c-article-supplementary__item" data-test="supp-item" id="MOESM23"><h3 class="c-article-supplementary__title u-h3"><a class="print-link" data-track="click" data-track-action="view supplementary info" data-test="supp-info-link" data-track-label="supplementary table s8" href="https://static-content.springer.com/esm/art%3A10.1038%2Fnature04209/MediaObjects/41586_2005_BFnature04209_MOESM23_ESM.xls" data-supp-info-image="">Supplementary Table S8</a></h3><div class="c-article-supplementary__description" data-component="thumbnail-container"><p>Potentially novel associations of proteins with genetic disorders as revealed by the CCSB-HI1 interaction data set. (XLS 89 kb)</p></div></div></div></div></div></section><section data-title="Rights and permissions"><div class="c-article-section" id="rightslink-section"><h2 class="c-article-section__title js-section-title js-c-reading-companion-sections-item" id="rightslink">Rights and permissions</h2><div class="c-article-section__content" id="rightslink-content"><p class="c-article-rights"><a data-track="click" data-track-action="view rights and permissions" data-track-label="link" href="https://s100.copyright.com/AppDispatchServlet?title=Towards%20a%20proteome-scale%20map%20of%20the%20human%20protein%E2%80%93protein%20interaction%20network&author=Jean-Fran%C3%A7ois%20Rual%20et%20al&contentID=10.1038%2Fnature04209&copyright=Springer%20Nature%20Limited&publication=0028-0836&publicationDate=2005-09-28&publisherName=SpringerNature&orderBeanReset=true">Reprints and permissions</a></p></div></div></section><section aria-labelledby="article-info" data-title="About this article"><div 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Towards a proteome-scale map of the human protein–protein interaction network | Nature