hReg-CNCC reconstructs a regulatory network in human cranial neural crest cells and annotates variants in a developmental context | |
Feng, Zhanying1,11; Duren, Zhana9,10; Xiong, Ziyi2,4,8; Wang, Sijia3,7; Liu, Fan2,5; Wong, Wing Hung9; Wang, Yong1,6,7,11 | |
刊名 | COMMUNICATIONS BIOLOGY |
2021-04-06 | |
卷号 | 4期号:1页码:16 |
DOI | 10.1038/s42003-021-01970-0 |
英文摘要 | Cranial Neural Crest Cells (CNCC) originate at the cephalic region from forebrain, midbrain and hindbrain, migrate into the developing craniofacial region, and subsequently differentiate into multiple cell types. The entire specification, delamination, migration, and differentiation process is highly regulated and abnormalities during this craniofacial development cause birth defects. To better understand the molecular networks underlying CNCC, we integrate paired gene expression & chromatin accessibility data and reconstruct the genome-wide human Regulatory network of CNCC (hReg-CNCC). Consensus optimization predicts high-quality regulations and reveals the architecture of upstream, core, and downstream transcription factors that are associated with functions of neural plate border, specification, and migration. hReg-CNCC allows us to annotate genetic variants of human facial GWAS and disease traits with associated cis-regulatory modules, transcription factors, and target genes. For example, we reveal the distal and combinatorial regulation of multiple SNPs to core TF ALX1 and associations to facial distances and cranial rare disease. In addition, hReg-CNCC connects the DNA sequence differences in evolution, such as ultra-conserved elements and human accelerated regions, with gene expression and phenotype. hReg-CNCC provides a valuable resource to interpret genetic variants as early as gastrulation during embryonic development. The network resources are available at https://github.com/AMSSwanglab/hReg-CNCC. Zhanying Feng et al. present hReg-CNCC, a high-quality gene regulatory network for human cranial neural crest cells (CNCCs) constructed by consensus optimization modeling. It may be useful in interpreting genetic variants involved in embryonic development by linking the cis-regulatory sequences in this network with GWAS SNPs, disease risk loci, and evolutionarily-conserved regions of the genome. |
资助项目 | Shanghai Municipal Science and Technology Major Project[2017SHZDZX01] ; CAS Light of West China Program[xbzg-zdsys-201913] ; CAS Interdisciplinary Innovation Team project, National Key R&D Program of China[2017YFC0908400] ; CAS Interdisciplinary Innovation Team project, National Key R&D Program of China[2020YFA0712402] ; National Natural Science Foundation of China (NSFC)[12025107] ; National Natural Science Foundation of China (NSFC)[11871463] ; National Natural Science Foundation of China (NSFC)[61621003] ; National Natural Science Foundation of China (NSFC)[91651507] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDC01000000] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDB38010400] ; China Scholarship Council PhD Fellowship ; NIH[P50-HG007735] ; NIH[R01HG010359] |
WOS研究方向 | Life Sciences & Biomedicine - Other Topics ; Science & Technology - Other Topics |
语种 | 英语 |
出版者 | NATURE RESEARCH |
WOS记录号 | WOS:000637808400003 |
内容类型 | 期刊论文 |
源URL | [http://ir.amss.ac.cn/handle/2S8OKBNM/58463] |
专题 | 应用数学研究所 |
通讯作者 | Liu, Fan; Wong, Wing Hung; Wang, Yong |
作者单位 | 1.Chinese Acad Sci, Acad Math & Syst Sci, Natl Ctr Math & Interdisciplinary Sci, CEMS,NCMIS,MDIS, Beijing, Peoples R China 2.Chinese Acad Sci, Beijing Inst Genom, CAS Key Lab Genom & Precis Med, Beijing, Peoples R China 3.Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Key Lab Computat Biol, Shanghai, Peoples R China 4.Erasmus MC Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands 5.Chinese Acad Sci, China Natl Ctr Bioinformat, Beijing, Peoples R China 6.Chinese Acad Sci, Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Key Lab Syst Biol, Hangzhou, Peoples R China 7.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China 8.Erasmus MC Univ Med Ctr Rotterdam, Dept Genet Identificat, Rotterdam, Netherlands 9.Stanford Univ, Bio X Program, Dept Biomed Data Sci, Dept Stat, Stanford, CA 94305 USA 10.Clemson Univ, Dept Genet & Biochem, Ctr Human Genet, Greenwood, SC USA |
推荐引用方式 GB/T 7714 | Feng, Zhanying,Duren, Zhana,Xiong, Ziyi,et al. hReg-CNCC reconstructs a regulatory network in human cranial neural crest cells and annotates variants in a developmental context[J]. COMMUNICATIONS BIOLOGY,2021,4(1):16. |
APA | Feng, Zhanying.,Duren, Zhana.,Xiong, Ziyi.,Wang, Sijia.,Liu, Fan.,...&Wang, Yong.(2021).hReg-CNCC reconstructs a regulatory network in human cranial neural crest cells and annotates variants in a developmental context.COMMUNICATIONS BIOLOGY,4(1),16. |
MLA | Feng, Zhanying,et al."hReg-CNCC reconstructs a regulatory network in human cranial neural crest cells and annotates variants in a developmental context".COMMUNICATIONS BIOLOGY 4.1(2021):16. |
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