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表观组学小组长有话说

王HH 生信技能树 2022-06-07

Gene expression can be controlled through the action of repressor proteins that attach to silencer regions of the DNA. These epigenetic changes may last through cell divisions for the duration of the cell's life, and may also last for multiple generations even though they do not involve changes in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or "express themselves") differently. [1]

epiGroup 总结和更新

自从群主从1月份组建小分队以来,除了一开始的查资料到后来就不了了之,总结原因一是因为自己不够勤奋好学,另一方面则是缺乏一套可行的方法更系统地学习computational epigenetics. 所以问题还是归结到如何自律自主并且系统学习计算表观遗传学。

学什么,怎么学?

知识

Stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence

1. 记录并理解一些常见的概念&技术原理

感觉做表观这些应该是必知的,也可以归纳到技能部分边练边学

  • DNA methylation 常见的reader, writer, eraser列表

  • Histone modification 同DNA methylation

  • ChIP-seq: 目前lab最最常用的技术了,大致就是通过免疫共沉淀的方法找到和某感兴趣蛋白或者修饰(通过识别该修饰的蛋白IP实现的)在基因组上的富集情况,即亲和位点

  • WGBS

2. Specific epigenetic processes

由于实验室主要做干细胞相关的如DNA methylation reprogramming, imprinting, 就稍微了解一点,但是其他的似乎也很有趣!

  • paramutation,

  • bookmarking,

  • imprinting,

  • gene silencing,

  • X chromosome inactivation,

  • position effect,

  • DNA methylation reprogramming,

  • transvection,

  • maternal effects,

  • the progress of carcinogenesis,

  • many effects of teratogens,

  • regulation of histone modifications and heterochromatin,

  • and technical limitations affecting parthenogenesis and cloning

实战技能

内容和要求

另一方面,出于practical 的需要,打算从实践文章开始深入理解表观遗传学。google了一下发现2016年CELL推出了Internaltional Human Epigenome Consortium, 刚好适合有过高通量测序相关科研经验小菜鸟的升级。这套文章集合分析人体组织的表观遗传数据,并且用新的分析方法在细胞机制层面研究复杂人类疾病。从文章比例看,相比发育和免疫应答相关的研究,神经、血液类疾病和癌症的方面还是相对少一点(是采样困难?发育和免疫的研究也相对成熟一些?)。

至于书籍课本,个人感觉等要用了再系统查也是OK的。

21 papers across Cell Press journals, in 2016, Nov

Illuminate how changes to chromatin contribute to cell-type-specific biology, development, variation between individuals, and disease.

This one-of-a-kind, open access collection comprises 24 papers published in Cell and other Cell Press journals plus 17 papers published elsewhere. The collection offers readers epigenetic datasets for primary human tissues and analyses from researchers around the globe studying the cellular mechanisms associated with complex human disease. We hope you will enjoy exploring the Cell Press articles with this interactive graphic. A complete list of all the consortium papers published is available below the graphic. [^2]

文章分类与学习计划

自己更感兴趣的是3,4 两部分, 团队的话大家各分一篇文章去实践,完事后需要总结文章到博客或者技能树,先理解,再去实现代码,计划21天一篇文章,21天养成一个好习惯,下面是部分文献推荐列表:

  1. Noncoding DNA variants in disease, 5

  • The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease

  • Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

  • Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters

  • Histone Acetylome-wide Association Study of Autism Spectrum Disorder

  • A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome

  • Pathways involved in cell fate determination and disease, 9

    • β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance

    • Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity - Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways

    • Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells - Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

    • CD8+ T Cells from Human Neonates Are Biased toward an Innate Immune Response - The Hematopoietic Transcription Factors RUNX1 and ERG Prevent AML1-ETO Oncogene Overexpression and Onset of the Apoptosis Program in t(8;21) AMLs - Analysis of Normal Human Mammary Epigenomes Reveals Cell-Specific Active Enhancer States and Associated Transcription Factor Networks - Distinct Trends of DNA Methylation Patterning in the Innate and Adaptive Immune Systems 

  • Computational tools, 5

    • eFORGE: A Tool for Identifying Cell Type-Specific Signal in Epigenomic Data

    • The International Human Epigenome Consortium Data Portal

    • The BLUEPRINT Data Analysis Portal - Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs - Soft X-Ray Tomography Reveals Gradual Chromatin Compaction and Reorganization during Neurogenesis In Vivo 

  • Identifying heterogeneity in epigenomic measurements, 5

    • DNA Methylation Dynamics of Human Hematopoietic Stem Cell Differentiation(mark先:))

    • Nucleosome Density ChIP-Seq Identifies Distinct Chromatin Modification Signatures Associated with MNase Accessibility

    • Epigenomic Deconvolution of Breast Tumors Reveals Metabolic Coupling between Constituent Cell Types

    • Decoding the DNA Methylome of Mantle Cell Lymphoma in the Light of the Entire B Cell Lineage

      

    [^1]: "Epigenetics", from Wikipedia [2]: IHEC

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