{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:01:47Z","timestamp":1791230507623,"version":"4.1.0"},"reference-count":51,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"50","funder":[{"name":"Collaborative Research Fund","award":["C7165-20GF"],"award-info":[{"award-number":["C7165-20GF"]}]},{"name":"General Research Fund","award":["17303123"],"award-info":[{"award-number":["17303123"]}]},{"name":"General Research Fund","award":["17307919"],"award-info":[{"award-number":["17307919"]}]},{"name":"Shaanxi Provincial Key Research and Development Program","award":["2025GH-YBXM-031"],"award-info":[{"award-number":["2025GH-YBXM-031"]}]},{"name":"Young Talent Support Plan of Xi an Jiaotong University","award":["YQ6J001"],"award-info":[{"award-number":["YQ6J001"]}]},{"name":"RGC Senior Research Fellow","award":["SRFS2425-7S04"],"award-info":[{"award-number":["SRFS2425-7S04"]}]},{"name":"Theme-based Research Schemes","award":["T11-705\/21-N"],"award-info":[{"award-number":["T11-705\/21-N"]}]},{"name":"Shaanxi Sanqin Talent Program","award":["2024SYJ20"],"award-info":[{"award-number":["2024SYJ20"]}]},{"name":"Health@InnoHK Innovation and Technology Commission program of the Hong Kong SAR Government"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,12,12]]},"abstract":"<jats:p>Mapping the interaction potential of different variant combinations of viral antigens and human cell receptors and understanding how viral antigen mutations interact with human genetic polymorphisms are critical for predicting infection susceptibility and informing precision public health strategies. Here, we develop a droplet-based single-cell pairing and library-on-library interaction screening (SPLIS) system for high-throughput profiling of the syncytium-formation landscapes of various spike\u2013angiotensin-converting enzyme 2 (ACE2) variant combinations. This system uses combined droplet sorting and merging to deterministically encapsulate one antigen-presenting sender cell and one receptor-expressing receiver cell into each drop, followed by selection and sequencing of the fused DNA readouts to characterize the syncytium-formation potential of each combination. We applied SPLIS to characterize both fusion-enhancing and -inhibiting variant pairs, comprehensively profiling how ACE2 single-nucleotide polymorphisms modulate susceptibility to emerging severe acute respiratory syndrome coronavirus 2 spike mutations. Our system emerges as a powerful tool to interrogate the interactions between two libraries of variants, offering valuable insights into host susceptibility patterns and viral infectivity trends.<\/jats:p>","DOI":"10.1126\/sciadv.aeb1515","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:58:57Z","timestamp":1765565937000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Droplet-based single-cell pairing for high-throughput interaction mapping of antigen-receptor combinations"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-2482","authenticated-orcid":true,"given":"Lang","family":"Nan","sequence":"first","affiliation":[{"name":"School of Instrument Science and Technology, Xi\u2019an Jiaotong University, Xi\u2019an, Shaanxi 710049, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2751-6565","authenticated-orcid":true,"given":"Charles W. F.","family":"Chan","sequence":"additional","affiliation":[{"name":"Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China."},{"name":"Centre for Oncology and Immunology, Hong Kong Science Park, Shatin, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3656-3952","authenticated-orcid":true,"given":"Bei","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China."},{"name":"Centre for Oncology and Immunology, Hong Kong Science Park, Shatin, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Han","sequence":"additional","affiliation":[{"name":"Advanced Biomedical Instrumentation Centre, Hong Kong Science Park, Shatin, Hong Kong SAR, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-9188","authenticated-orcid":true,"given":"Gigi C. 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