Dataset Information

Deep learning of the splicing (epi)genetic code reveals a novel candidate mechanism linking histone modifications to ESC fate decision.

ABSTRACT: Alternative splicing (AS) is a genetically and epigenetically regulated pre-mRNA processing to increase transcriptome and proteome diversity. Comprehensively decoding these regulatory mechanisms holds promise in getting deeper insights into a variety of biological contexts involving in AS, such as development and diseases. We assembled splicing (epi)genetic code, DeepCode, for human embryonic stem cell (hESC) differentiation by integrating heterogeneous features of genomic sequences, 16 histone modifications with a multi-label deep neural network. With the advantages of epigenetic features, DeepCode significantly improves the performance in predicting the splicing patterns and their changes during hESC differentiation. Meanwhile, DeepCode reveals the superiority of epigenomic features and their dominant roles in decoding AS patterns, highlighting the necessity of including the epigenetic properties when assembling a more comprehensive splicing code. Moreover, DeepCode allows the robust predictions across cell lineages and datasets. Especially, we identified a putative H3K36me3-regulated AS event leading to a nonsense-mediated mRNA decay of BARD1. Reduced BARD1 expression results in the attenuation of ATM/ATR signalling activities and further the hESC differentiation. These results suggest a novel candidate mechanism linking histone modifications to hESC fate decision. In addition, when trained in different contexts, DeepCode can be expanded to a variety of biological and biomedical fields.

SUBMITTER: Xu Y

PROVIDER: S-EPMC5716079 | biostudies-other | 2017 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Deep learning of the splicing (epi)genetic code reveals a novel candidate mechanism linking histone modifications to ESC fate decision.

Xu Yungang Y Wang Yongcui Y Luo Jiesi J Zhao Weiling W Zhou Xiaobo X

Nucleic acids research 20171201 21

Alternative splicing (AS) is a genetically and epigenetically regulated pre-mRNA processing to increase transcriptome and proteome diversity. Comprehensively decoding these regulatory mechanisms holds promise in getting deeper insights into a variety of biological contexts involving in AS, such as development and diseases. We assembled splicing (epi)genetic code, DeepCode, for human embryonic stem cell (hESC) differentiation by integrating heterogeneous features of genomic sequences, 16 histone ...[more]

PMID: 29036709

Similar Datasets

Project description:Aim:To evaluate two different techniques of cross-linking: standard epithelium-off (CXL epi-off) versus transepithelial (CXL epi-on) cross-linking in patient with progressive keratoconus. Methods:Forty eyes from 32 patients with progressive keratoconus were prospectively enrolled from June 2014 to June 2015 in this nonblinded, randomized comparative study. Twenty eyes were treated by CXL epi-off and 20 by CLX epi-on, randomly assigned, and followed for 2 years. All patients underwent a complete ophthalmologic testing that included uncorrected and best corrected visual acuity, central and peripheral corneal thickness, corneal astigmatism, simulated maximum, minimum, and average keratometry, corneal confocal microscopy, Schirmer I and break-up time (BUT) tests, and the Ocular Surface Disease Index. Intra- and postoperative complications were recorded. The solution used for CXL epi-off comprised riboflavin 0.1% and dextran 20.0% (Ricrolin), whereas the solution for CXL epi-on (Ricrolin TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with a UV-X system at 3?mW/cm2. Results:In both groups, a significant improvement in visual function (Group 1: baseline 0.36?±?0.16 logMAR, two-year follow-up 0.22?±?0.17 logMAR, p=0.01; Group 2: baseline 0.32?±?0.18 logMAR, 2-year follow-up 0.27?±?0.19 logMAR, p=0.01) was recorded. Keratometry remained unchanged in both groups. The mean corneal thickness showed a significant reduction (mean difference of corneal thickness: -55 micron and -71 micron, resp.). One-month after treatment, OSDI© reached 13.56?±?2.15 in Group 1 (p=0.03) and 11.26?±?2.12 in Group 2 (p=0.04). At confocal microscopy, abnormal corneal nerve alterations were found in both groups. Fibrotic reaction (43.75%) and activated keratocyte (62.6%) were more commonly recorded in Group 1 than in Group 2 (25.0% and 18.75%), with p=0.668 and 0.356, respectively. Conclusion:Our findings demonstrate that both procedures are able to slow keratoconus progression. Both treatment modalities are equivalent in terms of results and related complications. CXL epi-on technique is preferable to CXL epi-off since it preserves the corneal thickness and improves visual acuity, also reducing the postoperative ocular discomfort during the study period.

Dataset Information

Deep learning of the splicing (epi)genetic code reveals a novel candidate mechanism linking histone modifications to ESC fate decision.

Publications

Deep learning of the splicing (epi)genetic code reveals a novel candidate mechanism linking histone modifications to ESC fate decision.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets