Mapping disease regulatory circuits at cell-type resolution from single-cell multiomics data.
Mapping disease regulatory circuits at cell-type resolution from single-cell multiomics data.
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DOI：
10.1038/s43588-023-00476-5
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发表时间：
2023-07
期刊：
影响因子：
--
通讯作者：
Sealfon, Stuart C.
中科院分区：
文献类型：
--
作者：
Chen, Xi;Wang, Yuan;Cappuccio, Antonio;Cheng, Wan-Sze;Zamojski, Frederique Ruf;Nair, Venugopalan D.;Miller, Clare M.;Rubenstein, Aliza B.;Nudelman, German;Tadych, Alicja;Theesfeld, Chandra L.;Vornholt, Alexandria;George, Mary-Catherine;Ruffin, Felicia;Dagher, Michael;Chawla, Daniel G.;Soares-Schanoski, Alessandra;Spurbeck, Rachel R.;Ndhlovu, Lishomwa C.;Sebra, Robert;Kleinstein, Steven H.;Letizia, Andrew G.;Ramos, Irene;Fowler Jr, Vance G.;Woods, Christopher W.;Zaslavsky, Elena;Troyanskaya, Olga G.;Sealfon, Stuart C.
Resolving chromatin-remodeling-linked gene expression changes at cell-type resolution is important for understanding disease states. Here we describe MAGICAL (Multiome Accessibility Gene Integration Calling and Looping), a hierarchical Bayesian approach that leverages paired single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing from different conditions to map disease-associated transcription factors, chromatin sites, and genes as regulatory circuits. By simultaneously modeling signal variation across cells and conditions in both omics data types, MAGICAL achieved high accuracy on circuit inference. We applied MAGICAL to study Staphylococcus aureus sepsis from peripheral blood mononuclear single-cell data that we generated from subjects with bloodstream infection and uninfected controls. MAGICAL identified sepsis-associated regulatory circuits predominantly in CD14 monocytes, known to be activated by bacterial sepsis. We addressed the challenging problem of distinguishing host regulatory circuit responses to methicillin-resistant and methicillin-susceptible S. aureus infections. Although differential expression analysis failed to show predictive value, MAGICAL identified epigenetic circuit biomarkers that distinguished methicillin-resistant from methicillin-susceptible S. aureus infections.
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影响因子：
14.9
作者：
Gillespie M;Jassal B;Stephan R;Milacic M;Rothfels K;Senff-Ribeiro A;Griss J;Sevilla C;Matthews L;Gong C;Deng C;Varusai T;Ragueneau E;Haider Y;May B;Shamovsky V;Weiser J;Brunson T;Sanati N;Beckman L;Shao X;Fabregat A;Sidiropoulos K;Murillo J;Viteri G;Cook J;Shorser S;Bader G;Demir E;Sander C;Haw R;Wu G;Stein L;Hermjakob H;D'Eustachio P
通讯作者：
D'Eustachio P
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
64.5
作者：
Gasperini, Molly;Hill, Andrew J.;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
5.8
作者：
Gjertsson, I;Hultgren, OH;Tarkowski, A
通讯作者：
Tarkowski, A
DOI：
10.1126/science.aau0730
发表时间：
2018-09-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cao J;Cusanovich DA;Ramani V;Aghamirzaie D;Pliner HA;Hill AJ;Daza RM;McFaline-Figueroa JL;Packer JS;Christiansen L;Steemers FJ;Adey AC;Trapnell C;Shendure J
通讯作者：
Shendure J