近日，國(guó)際期刊《核酸研究》Nucleic Acids Research上刊登了華中科技大學(xué)生命科學(xué)與技術(shù)學(xué)院郭安源課題組的研究成果,，研究者報(bào)告了關(guān)于急性T淋巴細(xì)胞白血病中miRNA和轉(zhuǎn)錄因子共調(diào)控網(wǎng)絡(luò)的生物信息學(xué)研究最新成果,，并在此基礎(chǔ)上與同濟(jì)醫(yī)學(xué)院教授孫軍和協(xié)和醫(yī)院血液科教授陳智超合作,，對(duì)其中的核心調(diào)控模塊進(jìn)行了實(shí)驗(yàn)驗(yàn)證。
據(jù)了解,，急性T淋巴細(xì)胞白血?。═-ALL）是一種惡性血液疾病，由未分化或分化很差的淋巴細(xì)胞在造血組織（特別是骨髓,、脾臟和淋巴結(jié)）無限增殖所致,，多發(fā)于兒童和青少年,。盡管近年來多藥聯(lián)合、大劑量化療等治療手段不斷改進(jìn),，以及各類造血干細(xì)胞移植得到應(yīng)用和推廣，但是其治療效果和預(yù)后比更常見的B細(xì)胞系淋巴細(xì)胞白血病仍然要差很多,。目前,，關(guān)于急性T淋巴細(xì)胞白血病的具體分子機(jī)理和調(diào)控機(jī)理還不清楚。
郭安源課題組以miRNA和轉(zhuǎn)錄因子的共調(diào)控角度為切入點(diǎn),，運(yùn)用生物信息學(xué)方法,，預(yù)測(cè)miRNA和轉(zhuǎn)錄因子與疾病基因之間形成的共調(diào)控前饋環(huán)模塊，并由此構(gòu)建共調(diào)控網(wǎng)絡(luò),。通過深入分析該調(diào)控網(wǎng)絡(luò),，研究人員獲得了其中的核心miRNA和基因，并進(jìn)一步對(duì)其中核心基因miR-19與CYLD在T-ALL中的分子機(jī)理進(jìn)行了研究,，首次揭示了miR-19抑制CYLD蛋白的產(chǎn)生,，繼而激活下游的NFKB信號(hào)通路，導(dǎo)致T淋巴細(xì)胞增殖失控,。
該研究成果從系統(tǒng)網(wǎng)絡(luò)水平上研究了急性T淋巴細(xì)胞白血病的發(fā)病機(jī)理和調(diào)控過程,，為其診斷和治療提供了理論依據(jù)，同時(shí)為復(fù)雜疾病的研究提供了計(jì)算和實(shí)驗(yàn)交叉的新思路和方法,。
據(jù)悉,，郭安源主要從事生物信息學(xué)和系統(tǒng)生物學(xué)在復(fù)雜疾病中的研究，包括數(shù)據(jù)整合,、數(shù)據(jù)庫(kù)構(gòu)建,、miRNA調(diào)控、比較基因組學(xué)和二代測(cè)序數(shù)據(jù)的分析研究等,。（生物谷Bioon.com）
doi:10.1093/nar/gkr965
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AnimalTFDB: a comprehensive animal transcription factor database
Hong-Mei Zhang1, Hu Chen1, Wei Liu1, Hui Liu1, Jing Gong1, Huili Wang2 and An-Yuan Guo1,*
Transcription factors (TFs) are proteins that bind to specific DNA sequences, thereby playing crucial roles in gene-expression regulation through controlling the transcription of genetic information from DNA to RNA. Transcription cofactors and chromatin remodeling factors are also essential in the gene transcriptional regulation. Identifying and annotating all the TFs are primary and crucial steps for illustrating their functions and understanding the transcriptional regulation. In this study, based on manual literature reviews, we collected and curated 72 TF families for animals, which is currently the most complete list of TF families in animals. Then, we systematically characterized all the TFs in 50 animal species and constructed a comprehensive animal TF database, AnimalTFDB. To better serve the community, we provided detailed annotations for each TF, including basic information, gene structure, functional domain, 3D structure hit, Gene Ontology, pathway, protein–protein interaction, paralogs, orthologs, potential TF-binding sites and targets. In addition, we collected and annotated transcription cofactors and chromatin remodeling factors. AnimalTFDB has a user-friendly web interface with multiple browse and search functions, as well as data downloading. It is freely available at http://www.bioguo.org/AnimalTFDB/.
