{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T19:30:35Z","timestamp":1783625435237,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":285,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Recent advances in generating massive single\u2010cell\/nucleus transcriptomic data have shown great potential for facilitating the identification of cell type\u2013specific Alzheimer's disease (AD) pathobiology and drug\u2010target discovery for therapeutic development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We developed The Alzheimer's Cell Atlas (TACA) by compiling an AD brain cell atlas consisting of over 1.1 million cells\/nuclei across 26 data sets, covering major brain regions (hippocampus, cerebellum, prefrontal cortex, and so on) and cell types (astrocyte, microglia, neuron, oligodendrocytes, and so on). We conducted nearly 1400 differential expression comparisons to identify cell type\u2013specific molecular alterations (e.g., case vs healthy control, sex\u2010specific, apolipoprotein E (\n                      <jats:italic>APOE<\/jats:italic>\n                      ) \u03b54\/\u03b54, and TREM2 mutations). Each comparison was followed by protein\u2010protein interaction module detection, functional enrichment analysis, and omics\u2010informed target and drug (over 700,000 perturbation profiles) screening. Over 400 cell\u2010cell interaction analyses using 6000 ligand\u2010receptor interactions were conducted to identify the cell\u2010cell communication networks in AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All results are integrated into TACA (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/taca.lerner.ccf.org\/\">https:\/\/taca.lerner.ccf.org\/<\/jats:ext-link>\n                      ), a new web portal with cell type\u2013specific, abundant transcriptomic information, and 12 interactive visualization tools for AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We envision that TACA will be a highly valuable resource for both basic and translational research in AD, as it provides abundant information for AD pathobiology and actionable systems biology tools for drug discovery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>We compiled an Alzheimer's disease (AD) brain cell atlas consisting of more than 1.1 million cells\/nuclei transcriptomes from 26 data sets, covering major brain regions (cortex, hippocampus, cerebellum) and cell types (e.g., neuron, oligodendrocyte, astrocyte, and microglia).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            We conducted over 1400 differential expression (DE) comparisons to identify cell type\u2013specific gene expression alterations. Major comparison types are (1) AD versus healthy control; (2) sex\u2010specific DE, (3) genotype\u2010driven DE (i.e., apolipoprotein E [\n                            <jats:italic>APOE<\/jats:italic>\n                            ] \u03b54\/\u03b54\u00a0vs\n                            <jats:italic>APOE<\/jats:italic>\n                            \u03b53\/\u03b53; TREM2\n                            <jats:sup>R47H<\/jats:sup>\n                            vs common variants) analysis; and (4) others. Each comparison was further followed by (1) human protein\u2010protein interactome network module analysis, (2) pathway enrichment analysis, and (3) gene\u2010set enrichment analysis.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>For drug screening, we conducted gene set enrichment analysis for all the comparisons with over 700,000 drug perturbation profiles connecting more than 10,000 human genes and 13,000 drugs\/compounds.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A total of over 400 analyses of cell\u2010cell interactions against 6000 experimentally validated ligand\u2010receptor interactions were conducted to reveal the disease\u2010relevant cell\u2010cell communications in AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.12350","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T07:00:16Z","timestamp":1665644416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["The Alzheimer's Cell Atlas (TACA): A single\u2010cell molecular map for translational therapeutics accelerator in Alzheimer's disease"],"prefix":"10.1002","volume":"8","author":[{"given":"Yadi","family":"Zhou","sequence":"first","affiliation":[{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jielin","family":"Xu","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute Lerner Research Institute Cleveland Clinic  Cleveland Ohio 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