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文章一：DeepCpG:能正确预计单细胞DNA甲基化水平的方法 DeepCpG: accurate prediction of single-cell DNA methylation states using deep learning Christof Angermueller,Heather J.Lee, Wolf Reik and Oliver Stegle http://genomebiology./articles/10.1186/s13059-017-1189-z 【导读】一个技术的长板往往也是产生短板的原因，单细胞有限的物质信息使单细胞甲基化测序的覆盖程度相对较低。通常的信息处理手段是将生物信息与模型建立分离。DeepCpG使用两者结合的学习模型来预测单细胞测序数据中甲基化改变。通过测试人与小鼠的单细胞甲基化数据，该方法显示出优越的表现。 Abstract Recent technological advances have enabledDNA methylation to be assayed at single-cell resolution. However, current protocols are limited by incomplete CpG coverage and hence methods to predict missing methylation states are critical to enable genome-wide analyses. We report DeepCpG, a computational approach based on deep neural networks topredict methylation states in single cells. We evaluate DeepCpG on single-cellmethylation data from five cell types generated using alternative sequencing protocols. DeepCpG yields substantially more accurate predictions than previousmethods. Additionally, we show that the model parameters can be interpreted,thereby providing insights into how sequence composition affects methylation variability. 文章二：小鼠模型的多组织表观遗传“时钟” Multi-tissue DNA methylation age predictor in mouse Thomas M. Stubbs,Marc Jan Bonder, Anne-Katrien Stark, Felix Krueger, BI Ageing Clock Team, Ferdinandvon Meyenn, Oliver Stegle and Wolf Reik http://genomebiology./articles/10.1186/s13059-017-1203-5 【导读】这是我们一系列四篇“时钟”论文的最后一篇。这个“时钟”的计算误差在3.33周，数据取自小鼠肝、脑、心、肺四个组织。这个时钟看似精准度比我们发表的第一个“时钟”要高，而且覆盖多组织，为什么我们还要坚持发表两周前的那个误差在6个月的“时钟”呢？科学研究常常由于执行者的实验设计理念不同、取材可行性不同产生不同的结果。本周的这一工作，取材到41周大的小鼠，所以这一误差值是基于相对年轻的小鼠计算结果，与前一个“时钟”在年龄跨度到26个月的老年鼠的误差值没有可比性。根据同样的两位业内专家评审意见，两个“时钟”各有特色，我们希望这一系列的“时钟”能为领域内衰老和老年疾病的表观遗传学研究提供有用的资讯。 Abstract Background: DNA methylation changes at adiscrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more experimentally tractable mouse. Results: We have generated a comprehensiveset of genome-scale base-resolution methylation maps from multiple mouse tissues spanning a wide range of ages. Many CpG sites show significant tissue-independent correlations with age which allowed us to develop amulti-tissue predictor of age in the mouse. Our model, which estimates agebased on DNA methylation at 329 unique CpG sites, has a median absolute error of 3.33 weeks and has similar properties to the recently described human epigenetic clock. Using publicly available datasets, we find that the mouseclock is accurate enough to measure effects on biological age, including in the context of interventions. While females and males show no significant differences in predicted DNA methylation age, ovariectomy results insignificant age acceleration in females. Furthermore, we identify significant differences in age-acceleration dependent on the lipid content of the diet. Conclusions: Here we identify andcharacterise an epigenetic predictor of age in mice, the mouse epigenetic clock. This clock will be instrumental for understanding the biology of ageingand will allow modulation of its ticking rate and resetting the clock in vivo to study the impact on biological age.
文章三：拟南芥的 H2A 单泛素化与 LHP1或 PRC2活性无关 H2A monoubiquitination in Arabidopsis thaliana is generally independent of LHP1 and PRC2 activity Yue Zhou, FranciscoJ. Romero-Campero, ángeles Gómez-Zambrano, Franziska Turck and Myriam Calonje http://genomebiology./articles/10.1186/s13059-017-1197-z 【导读】一个大家普遍接受的动物界模型是PcG复合体与H3K27me3结合再下一步介导H2A的单泛素化，这个模型在植物界被借鉴，但是一直没有确凿的证据。本周这一工作通过全基因组筛选拟南芥PcG的突变体，发现PRC2或是H3K27me3并不是H2A单泛素化的上游条件， H3K27me3 和 LHP1的存在也不是H2AK121ub的先决条件。相对的AtBMI1才是拟南芥中建立H3K27me3上游因素之一。回答问题的同时，势必提出了更多问题，目前通过这一工作，我们还不知道AtBMI1是否只在H3K27me3相关基因处驻扎，还是还有其他功能参与完成下游修饰。这是我们植物表观遗传特刊的论文之一，更多的特刊论文将在五月与大家见面。 Abstract Background：Polycomb group complexes PRC1 and PRC2 repress gene expression at the chromatin level in eukaryotes. The classic recruitment model of Polycomb group complexes in whichPRC2-mediated H3K27 trimethylation recruits PRC1 for H2A monoubiquitination was recently challenged by data showing that PRC1 activity can also recruit PRC2.However, the prevalence of these two mechanisms is unknown, especially in plants as H2AK121ub marks were examined at only a handful of Polycomb group targets. Results：By using genome-wideanalyses, we show that H2AK121ub marks are surprisingly widespread in Arabidopsisthaliana, often co-localizing with H3K27me3 but also occupying a set oftranscriptionally active genes devoid of H3K27me3. Furthermore, by profiling H2AK121ub and H3K27me3 marks in atbmi1a/b/c, clf/swn,and lhp1mutants we found that PRC2 activity is not required forH2AK121ub marking at most genes. In contrast, loss of AtBMI1 function impactsthe incorporation of H3K27me3 marks at most Polycomb group targets. Conclusions：Our findings showthe relationship between H2AK121ub and H3K27me3 marks across the A.thaliana genome and unveil that ubiquitination by PRC1 is largely independent of PRC2 activity in plants, while the inverse is true for H3K27trimethylation. 文章四：METSIM人群中肠道微生物、血代谢产物以及代谢综合征的相关研究 Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort Elin Org, Yuna Blum,Silva Kasela, Margarete Mehrabian, Johanna Kuusisto, Antti J. Kangas,Pasi Soininen, Zeneng Wang, Mika Ala-Korpela, Stanley L. Hazen,Markku Laakso and Aldons J. Lusis http://genomebiology./articles/10.1186/s13059-017-1194-2 【导读】 METSIM 人群是一个芬兰代谢综合征男性人群。本文采用的是这一人群中的部分样本，531名中年男性，分析糖耐量、BMI 以及胰岛素抵抗等等表征与肠道微生物的关系。虽然类似的肠道微生物与代谢综合征研究在荷兰、比利时两个国家完成过，但是本文的优势在于对宿主血液代谢物的研究，把肠道微生物与宿主的代谢表征直接联系起来。同许多流行病研究相似，本文的发现并不能完全重复荷兰与比利时的研究成果，体现了芬兰人群的特异性。所以更强调了要找到人群中的普适规律，恐怕跨人群、跨种族的研究就越发重要。 Abstract Background: The gut microbiome is a complexand metabolically active community that directly influences host phenotypes. Inthis study, we profile gut microbiota using 16S rRNA gene sequencing in 531well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. Results: We investigate gut microbiotarelationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, includingfatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gutmicrobiota-dependent metabolite associated with coronary artery disease andstroke. We further investigate the gut microbiota composition andmicrobiota–metabolite relationships in subjects with different body mass indexand individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. Conclusions: Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host–gutmicrobiota relationships.
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