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与thalidomide相关的四肢和心脏缺陷有关的可能的新候选者:一个系统生物学方法

Bruna Duarte Rengel^1,2,3,4, Lavínia Schuler-Faccini^1,2,5,3, Lucas Rosa Fraga^5,3,6,4

¹Laboratory of Medical Genetics and Evolution, Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.

Biochemical genetics

|April 30, 2024

概括

塔利多米德的致死性可能涉及被破坏的HAND2和TBX5相互作用. 系统生物学发现EP300是一种关键蛋白质,与ZIC3,GLI1,GLI3,ZNF148,PRDM16,FANCB,ESCO2和XRCC2一起,可能导致心脏和四肢形.

科学领域:

发育生物学是发展生物学.
系统生物学系统生物学
甲状腺学甲状腺学

背景情况:

塔利多米德是一种已知的原体,可引起严重的心脏和四肢形.
塔利多米德致病性背后的精确分子机制仍然不完全理解.
最近的研究确定了TBX5作为thalidomide的标,并突出了被破坏的HAND2-TBX5相互作用.

研究的目的:

为了识别涉及thalidomide诱导的原性新型候选基因和蛋白质.
在暴露于thalidomide的背景下,研究HAND2和TBX5的相互作用网络.
为了将分子发现与观察到的心脏和四肢形相关联.

主要方法:

利用了系统生物学方法,整合了来自TF2DNA,REACTOME,人类现象型本体学和InterPro数据库的数据.
使用STRING和Cytoscape构建和分析交互网络,包括单独和组合的HAND2/TBX5和teratogenicity网络.
在thalidomide治疗后对基因表达综合数据进行差异基因表达 (DGE) 分析.

主要成果:

在所有分析的网络中,EP300蛋白是显著的因素.
在心脏和四肢形网络中发现了几种含有C2H2域的蛋白质 (ZIC3,GLI1,GLI3,ZNF148,PRDM16).
DGE分析显示,在用thalidomide处理的样本中,FANCB,ESCO2和XRCC2的下调,这些基因也存在于相关的形网络中.

结论:

系统生物学分析成功地确定了新型候选基因和蛋白质,这些基因和蛋白质与thalidomide的致性有关.
EP300被强调为进一步调查thalidomide对胚胎发育影响的特别有前途的候选人.
这项研究为了解thalidomide破坏的分子通路提供了基础,可能导致新的治疗或预防策略.

关键词:

生物信息学是一种生物信息学.生物网络是生物网络.发育生物学是发展生物学.EP300 EP300 在线播放基因基因基因基因基因基因

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