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Johnson, T. S.

Publications and source records attributed to Johnson, T. S..

2 recordsLinked to original sources

BURMUDA: A novel deep transfer learning method for single-cell RNA sequencing batch correction reveals hidden high-resolution cellular subtypes

To fully utilize the power of single-cell RNA sequencing (scRNA-seq) technologies for cell lineation and identifying bona fide transcriptional signals, it is necessary to combine data from multiple experiments. We present BERMUDA (Batch-Effect ReMoval Using Deep Autoencoders) -- a novel transfer-learning-based method for batch-effect correction in scRNA-seq data. BERMUDA effectively combines different batches of scRNA-seq data with vastly different cell population compositions and amplifies biological signals by transferring information among batches. We demonstrate that BERMUDA outperforms existing methods for removing batch effects and distinguishing cell types in multiple simulated and real scRNA-seq datasets.

bioinformatics

Integration of Mouse and Human Single-cell RNA Sequencing Infers Spatial Cell-type Composition in Human Brains

Technical advances have enabled the identification of high-resolution cell types within tissues based on single-cell transcriptomics. However, such analyses are restricted in human brain tissue due to the limited number of brain donors. In this study, we integrate mouse and human data to predict cell-type proportions in human brain tissue, and spatially map the resulting cellular composition. By applying feature selection and linear modeling, combinations of human and mouse brain single-cell transcriptomics profiles can be integrated to \"fill in\" missing information. These combined \"in silico chimeric\" datasets are used to model the composition of nine cell types in 3,702 human brain samples in six Allen Human Brain Atlas (AHBA) donors. Cell types were spatially consistent regardless of the scRNA-Seq dataset (91% significantly correlated) or AHBA donor (p-value = 4.43E-20 by t-test) used in the model. Importantly, neuron nuclei location and neuron mRNA location were correlated only after accounting for neural connectivity (p-value = 1.26E-10), which supports the notion that gene expression is a better indicator than nuclei location of cellular localization for cells with large and irregularly shaped cell bodies, such as neurons. These results advocate for the integration of mouse and human data in models of brain tissue heterogeneity.

bioinformatics