DeeReCT-TSS: A novel meta-learning-based method annotates TSS in multiple cell types based on DNA sequences and RNA-seq data
KAUST DepartmentComputational Bioscience Research Center (CBRC)
Computer Science Program
Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
Structural and Functional Bioinformatics Group
Permanent link to this recordhttp://hdl.handle.net/10754/669746
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AbstractAbstract The accurate annotation of transcription start sites (TSSs) and their usage is critical for the mechanistic understanding of gene regulation under different biological contexts. To fulfil this, on one hand, specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner. On the other hand, various computational tools have also been developed for in silico prediction of TSSs solely based on genomic sequences. Most of these computational tools cast the problem as a binary classification task on a balanced dataset and thus result in drastic false positive predictions when applied on the genome-scale. To address these issues, we present DeeReCT-TSS, a deep-learning-based method that is capable of TSSs identification across the whole genome based on both DNA sequences and conventional RNA-seq data. We show that by effectively incorporating these two sources of information, DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types. Furthermore, we develop a meta-learning-based extension for simultaneous transcription start site (TSS) annotation on 10 cell types, which enables the identification of cell-type-specific TSS. Finally, we demonstrate the high precision of DeeReCT-TSS on two independent datasets from the ENCODE project by correlating our predicted TSSs with experimentally defined TSS chromatin states. Our application, pre-trained models and data are available at https://github.com/JoshuaChou2018/DeeReCT-TSS_release.
CitationZhou, J., zhang, bin, Li, H., Zhou, L., Li, Z., Long, Y., … Gao, X. (2021). DeeReCT-TSS: A novel meta-learning-based method annotates TSS in multiple cell types based on DNA sequences and RNA-seq data. doi:10.21203/rs.3.rs-640669/v1
SponsorsWe apologize to all colleagues whose work could not be cited due to space constraints. We thank all past and present members in Structural and Functional Bioinformatics (SFB) Group for their constructive feedback on this project. We also thank Mohammed Saif for providing generous support on computational resources.
PublisherResearch Square Platform LLC
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