bioRxiv ScienceSearch

Biology subjects

Quang, D.

Publications and source records attributed to Quang, D..

3 recordsLinked to original sources

YAMDA: thousandfold speedup of EM-based motif discovery using deep learning libraries and GPU

MotivationMotif discovery in large biopolymer sequence datasets can be computationally demanding, presenting significant challenges for discovery in omics research. MEME, arguably one of the most popular motif discovery software, takes quadratic time with respect to dataset size, leading to excessively long runtimes for large datasets. Therefore, there is a demand for fast programs that can generate results of the same quality as MEME.\n\nResultsHere we describe YAMDA, a highly scalable motif discovery software package. It is built on Pytorch, a tensor computation deep learning library with strong GPU acceleration that is highly optimized for tensor operations that are also useful for motifs. YAMDA takes linear time to find motifs as accurately as MEME, completing in seconds or minutes, which translates to speedups over a thousandfold.\n\nAvailabilityYAMDA is freely available on Github (https://github.com/daquang/YAMDA)\n\nContactdaquang@umich.edu

bioinformatics

FactorNet: a deep learning framework for predicting cell type specific transcription factor binding from nucleotide-resolution sequential data

Due to the large numbers of transcription factors (TFs) and cell types, querying binding profiles of all TF/cell type pairs is not experimentally feasible, owing to constraints in time and resources. To address this issue, we developed a convolutional-recurrent neural network model, called FactorNet, to computationally impute the missing binding data. FactorNet trains on binding data from reference cell types to make accurate predictions on testing cell types by leveraging a variety of features, including genomic sequences, genome annotations, gene expression, and single-nucleotide resolution sequential signals, such as DNase I cleavage. To the best of our knowledge, this is the first deep learning method to study the rules governing TF binding at such a fine resolution. With FactorNet, a researcher can perform a single sequencing assay, such as DNase-seq, on a cell type and computationally impute dozens of TF binding profiles. This is an integral step for reconstructing the complex networks underlying gene regulation. While neural networks can be computationally expensive to train, we introduce several novel strategies to significantly reduce the overhead. By visualizing the neural network models, we can interpret how the model predicts binding which in turn reveals additional insights into regulatory grammar. We also investigate the variables that affect cross-cell type predictive performance to explain why the model performs better on some TF/cell types than others, and offer insights to improve upon this field. Our method ranked among the top four teams in the ENCODE-DREAM in vivo Transcription Factor Binding Site Prediction Challenge.

genomics

Understanding sequence conservation with deep learning

MotivationComparing the human genome to the genomes of closely related mammalian species has been a powerful tool for discovering functional elements in the human genome. Millions of conserved elements have been discovered. However, understanding the functional roles of these elements still remain a challenge, especially in noncoding regions. In particular, it is still unclear why these elements are evolutionarily conserved and what kind of functional elements are encoded within these sequences.\n\nResultsWe present a deep learning framework, called DeepCons, to uncover potential functional elements within conserved sequences. DeepCons is a convolutional neural net (CNN) that receives a short segment of DNA sequence as input and outputs the probability of the sequence of being evolutionary conserved. DeepCons utilizes hundreds of convolution kernels to detect features within DNA sequences, and automatically learns these kernels after training the CNN model using 887,577 conserved elements and a similar number of nonconserved elements in the human genome. On a balanced test dataset, DeepCons can achieve an accuracy of 75% in determining whether a sequence element is conserved or not, and the area under the ROC curve of 0.83, based on information from the human genome alone. We further investigate the properties of the learned kernels. Some kernels are directly related to well-known regulatory motifs corresponding to transcription factors. Many kernels show positional biases relative to transcriptional start sites or transcription end sites. But most of discovered kernels do not correspond to any known functional element, suggesting that they might represent unknown categories of functional elements. We also utilize DeepCons to annotate how changes at each individual nucleotide might impact the conservation properties of the surrounding sequences.\n\nAvailabilityThe source code of DeepCons and all the learned convolution kernels in motif format is publicly available online at https://github.com/uci-cbcl/DeepCons.\n\nContactxhx@ics.uci.edu

bioinformatics