We introduce AtacWorks ( https://github.com/clara-genomics/AtacWorks ), a method to denoise and identify accessible chromatin regions from low-coverage or low-quality ATAC-seq data. AtacWorks uses a deep neural network to learn a mapping between noisy ATAC-seq data and corresponding higher-coverage or higher-quality data. To demonstrate the utility of AtacWorks, we train a model on data from four blood cell types and show that this model accurately denoises and identifies peaks from low-coverage bulk sequencing of different individuals, cell types, and experimental conditions. Further, we show that the deep learning model can be generalized to denoise low-quality data, aggregate single-cell ATAC-seq profiles, and Tn5 insertion sites for transcription factor footprinting. Finally, we apply our deep learning approach to denoise single-cell ATAC-seq data from hematopoietic stem cells to identify differentially-accessible regulatory elements between rare lineage-primed cell subpopulations.
ATAC-seq is a widely-applied assay used to measure genome-wide chromatin accessibility; however, its ability to detect active regulatory regions can depend on the depth of sequencing coverage and the signal-to-noise ratio. Here we introduce AtacWorks, a deep learning toolkit to denoise sequencing coverage and identify regulatory peaks at base-pair resolution from low cell count, low-coverage, or low-quality ATAC-seq data. Models trained by AtacWorks can detect peaks from cell types not seen in the training data, and are generalizable across diverse sample preparations and experimental platforms. We demonstrate that AtacWorks enhances the sensitivity of single-cell experiments by producing results on par with those of conventional methods using ~10 times as many cells, and further show that this framework can be adapted to enable cross-modality inference of protein-DNA interactions. Finally, we establish that AtacWorks can enable new biological discoveries by identifying active regulatory regions associated with lineage priming in rare subpopulations of hematopoietic stem cells.
Poker is a family of card games that includes many varia- tions. We hypothesize that most poker games can be solved as a pattern matching problem, and propose creating a strong poker playing system based on a unified poker representa- tion. Our poker player learns through iterative self-play, and improves its understanding of the game by training on the results of its previous actions without sophisticated domain knowledge. We evaluate our system on three poker games: single player video poker, two-player Limit Texas Hold’em, and finally two-player 2-7 triple draw poker. We show that our model can quickly learn patterns in these very different poker games while it improves from zero knowledge to a competi- tive player against human experts. The contributions of this paper include: (1) a novel represen- tation for poker games, extendable to different poker vari- ations, (2) a Convolutional Neural Network (CNN) based learning model that can effectively learn the patterns in three different games, and (3) a self-trained system that signif- icantly beats the heuristic-based program on which it is trained, and our system is competitive against human expert players.
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