Predicting Splicing from Primary Sequence with Deep Learning

Cell, Journal Year: 2019, Volume and Issue: 176(3), P. 535 - 548.e24

Published: Jan. 1, 2019

Language: Английский

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Expanded encyclopaedias of DNA elements in the human and mouse genomes

Nature, Journal Year: 2020, Volume and Issue: 583(7818), P. 699 - 710

Published: July 29, 2020

Abstract The human and mouse genomes contain instructions that specify RNAs proteins govern the timing, magnitude, cellular context of their production. To better delineate these elements, phase III Encyclopedia DNA Elements (ENCODE) Project has expanded analysis cell tissue repertoires RNA transcription, chromatin structure modification, methylation, looping, occupancy by transcription factors RNA-binding proteins. Here we summarize efforts, which have produced 5,992 new experimental datasets, including systematic determinations across fetal development. All data are available through ENCODE portal ( https://www.encodeproject.org ), II 1 Roadmap Epigenomics 2 data. We developed a registry 926,535 339,815 candidate cis -regulatory covering 7.9 3.4% respective genomes, integrating selected datatypes associated with gene regulation, constructed web-based server (SCREEN; http://screen.encodeproject.org ) to provide flexible, user-defined access this resource. Collectively, an expansive resource for scientific community build understanding organization function genomes.

Language: Английский

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Lineage-specific and single-cell chromatin accessibility charts human hematopoiesis and leukemia evolution

Nature Genetics, Journal Year: 2016, Volume and Issue: 48(10), P. 1193 - 1203

Published: Aug. 15, 2016

Language: Английский

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Impact of cytosine methylation on DNA binding specificities of human transcription factors

Science, Journal Year: 2017, Volume and Issue: 356(6337)

Published: May 4, 2017

Positives and negatives of methylated CpG When the DNA bases cytosine guanine are next to each other, a methyl group is generally added pyrimidine, generating mCpG dinucleotide. This modification alters structure but can also affect function by inhibiting transcription factor (TF) binding. Yin et al. systematically analyzed effect methylation on binding 542 human TFs (see Perspective Hughes Lambert). In addition some TFs, they found that mCpGs promote others, particularly involved in development, such as homeodomain proteins. Science , this issue p. eaaj2239 ; see 489

Language: Английский

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Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Science, Journal Year: 2019, Volume and Issue: 365(6460)

Published: Sept. 26, 2019

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects established a reference map the architecture MS that includes 200 autosomal susceptibility variants outside major histocompatibility complex (MHC), one chromosome X variant, 32 within extended MHC. used an ensemble methods to prioritize 551 putative genes implicate innate adaptive pathways distributed across cellular components immune system. Using expression profiles from purified human microglia, we observed enrichment for in these brain-resident cells, suggesting may have role targeting autoimmune process central nervous system, although is most likely initially triggered by perturbation peripheral responses.

Language: Английский

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New insights into the immunopathogenesis of systemic lupus erythematosus

Nature Reviews Rheumatology, Journal Year: 2016, Volume and Issue: 12(12), P. 716 - 730

Published: Nov. 22, 2016

Language: Английский

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Multiplexed droplet single-cell RNA-sequencing using natural genetic variation

Nature Biotechnology, Journal Year: 2017, Volume and Issue: 36(1), P. 89 - 94

Published: Dec. 11, 2017

Language: Английский

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The role of regulatory variation in complex traits and disease

Nature Reviews Genetics, Journal Year: 2015, Volume and Issue: 16(4), P. 197 - 212

Published: Feb. 24, 2015

Language: Английский

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Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types

Nature Genetics, Journal Year: 2018, Volume and Issue: 50(4), P. 621 - 629

Published: April 1, 2018

Language: Английский

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Basset: learning the regulatory code of the accessible genome with deep convolutional neural networks

Genome Research, Journal Year: 2016, Volume and Issue: 26(7), P. 990 - 999

Published: May 3, 2016

The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance—deep convolutional neural networks (CNNs). We introduce open source package Basset to apply CNNs learn functional activity DNA sequences from genomics data. trained compendium accessible genomic sites mapped in 164 cell types DNase-seq, and demonstrate greater predictive accuracy than previous methods. predictions for change accessibility between variant alleles were far Genome-wide association study (GWAS) SNPs that are likely be causal relative nearby linkage disequilibrium them. With Basset, researcher can perform single sequencing assay their type interest simultaneously cell's chromatin code annotate every mutation genome its influence present latent potential accessibility. Thus, offers powerful computational interpret genome.

Language: Английский

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