Impact of regulatory variation across human iPSCs and differentiated cells
© 2018 Banovich et al.; Published by Cold Spring Harbor Laboratory Press..
Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression levels, chromatin accessibility, and DNA methylation. Our analysis focused on a comparison of inter-individual regulatory variation across cell types. While most cell-type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell-type-specific regulatory QTLs are in shared open chromatin. This observation motivated us to develop a deep neural network to predict open chromatin regions from DNA sequence alone. Using this approach, we were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell-type-specific chromatin accessibility.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2018 |
---|---|
Erschienen: |
2018 |
Enthalten in: |
Zur Gesamtaufnahme - volume:28 |
---|---|
Enthalten in: |
Genome research - 28(2018), 1 vom: 18. Jan., Seite 122-131 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Banovich, Nicholas E [VerfasserIn] |
---|
Links: |
---|
Themen: |
Chromatin |
---|
Anmerkungen: |
Date Completed 07.08.2018 Date Revised 15.11.2022 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1101/gr.224436.117 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM278738982 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM278738982 | ||
003 | DE-627 | ||
005 | 20231225021324.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2018 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1101/gr.224436.117 |2 doi | |
028 | 5 | 2 | |a pubmed24n0929.xml |
035 | |a (DE-627)NLM278738982 | ||
035 | |a (NLM)29208628 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Banovich, Nicholas E |e verfasserin |4 aut | |
245 | 1 | 0 | |a Impact of regulatory variation across human iPSCs and differentiated cells |
264 | 1 | |c 2018 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 07.08.2018 | ||
500 | |a Date Revised 15.11.2022 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a © 2018 Banovich et al.; Published by Cold Spring Harbor Laboratory Press. | ||
520 | |a Induced pluripotent stem cells (iPSCs) are an essential tool for studying cellular differentiation and cell types that are otherwise difficult to access. We investigated the use of iPSCs and iPSC-derived cells to study the impact of genetic variation on gene regulation across different cell types and as models for studies of complex disease. To do so, we established a panel of iPSCs from 58 well-studied Yoruba lymphoblastoid cell lines (LCLs); 14 of these lines were further differentiated into cardiomyocytes. We characterized regulatory variation across individuals and cell types by measuring gene expression levels, chromatin accessibility, and DNA methylation. Our analysis focused on a comparison of inter-individual regulatory variation across cell types. While most cell-type-specific regulatory quantitative trait loci (QTLs) lie in chromatin that is open only in the affected cell types, we found that 20% of cell-type-specific regulatory QTLs are in shared open chromatin. This observation motivated us to develop a deep neural network to predict open chromatin regions from DNA sequence alone. Using this approach, we were able to use the sequences of segregating haplotypes to predict the effects of common SNPs on cell-type-specific chromatin accessibility | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a Chromatin |2 NLM | |
700 | 1 | |a Li, Yang I |e verfasserin |4 aut | |
700 | 1 | |a Raj, Anil |e verfasserin |4 aut | |
700 | 1 | |a Ward, Michelle C |e verfasserin |4 aut | |
700 | 1 | |a Greenside, Peyton |e verfasserin |4 aut | |
700 | 1 | |a Calderon, Diego |e verfasserin |4 aut | |
700 | 1 | |a Tung, Po Yuan |e verfasserin |4 aut | |
700 | 1 | |a Burnett, Jonathan E |e verfasserin |4 aut | |
700 | 1 | |a Myrthil, Marsha |e verfasserin |4 aut | |
700 | 1 | |a Thomas, Samantha M |e verfasserin |4 aut | |
700 | 1 | |a Burrows, Courtney K |e verfasserin |4 aut | |
700 | 1 | |a Romero, Irene Gallego |e verfasserin |4 aut | |
700 | 1 | |a Pavlovic, Bryan J |e verfasserin |4 aut | |
700 | 1 | |a Kundaje, Anshul |e verfasserin |4 aut | |
700 | 1 | |a Pritchard, Jonathan K |e verfasserin |4 aut | |
700 | 1 | |a Gilad, Yoav |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Genome research |d 1996 |g 28(2018), 1 vom: 18. Jan., Seite 122-131 |w (DE-627)NLM085678031 |x 1549-5469 |7 nnns |
773 | 1 | 8 | |g volume:28 |g year:2018 |g number:1 |g day:18 |g month:01 |g pages:122-131 |
856 | 4 | 0 | |u http://dx.doi.org/10.1101/gr.224436.117 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 28 |j 2018 |e 1 |b 18 |c 01 |h 122-131 |