Exploring single-cell data with deep multitasking neural networks

被引:205
作者
Amodio, Matthew [1 ]
van Dijk, David [1 ,2 ]
Srinivasan, Krishnan [1 ]
Chen, William S. [3 ]
Mohsen, Hussein [4 ]
Moon, Kevin R. [5 ]
Campbell, Allison [3 ]
Zhao, Yujiao [6 ]
Wang, Xiaomei [6 ]
Venkataswamy, Manjunatha [7 ]
Desai, Anita [7 ]
Ravi, V. [7 ]
Kumar, Priti [8 ]
Montgomery, Ruth [6 ]
Wolf, Guy [9 ,10 ]
Krishnaswamy, Smita [1 ,2 ]
机构
[1] Yale Univ, Dept Comp Sci, POB 2158, New Haven, CT 06520 USA
[2] Yale Univ, Dept Genet, New Haven, CT 06520 USA
[3] Yale Univ, Sch Med, New Haven, CT USA
[4] Yale Univ, Computat Biol & Bioinformat, New Haven, CT USA
[5] Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA
[6] Yale Univ, Dept Rheumatol, New Haven, CT USA
[7] NIMHANS, Dept Neurovirol, Bangalore, Karnataka, India
[8] Yale Univ, Dept Microbial Pathogenesis, New Haven, CT USA
[9] Univ Montreal, Dept Math & Stat, Montreal, PQ, Canada
[10] Mila Quebec Artificial Intelligence Inst, Montreal, PQ, Canada
关键词
DELTA T-CELLS;
D O I
10.1038/s41592-019-0576-7
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
It is currently challenging to analyze single-cell data consisting of many cells and samples, and to address variations arising from batch effects and different sample preparations. For this purpose, we present SAUCIE, a deep neural network that combines parallelization and scalability offered by neural networks, with the deep representation of data that can be learned by them to perform many single-cell data analysis tasks. Our regularizations (penalties) render features learned in hidden layers of the neural network interpretable. On large, multi-patient datasets, SAUCIE's various hidden layers contain denoised and batch-corrected data, a low-dimensional visualization and unsupervised clustering, as well as other information that can be used to explore the data. We analyze a 180-sample dataset consisting of 11 million T cells from dengue patients in India, measured with mass cytometry. SAUCIE can batch correct and identify cluster-based signatures of acute dengue infection and create a patient manifold, stratifying immune response to dengue.
引用
收藏
页码:1139 / +
页数:12
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