多组学前沿技术专刊序言

后基因组时代,基因组学、转录组学、蛋白质组学及代谢组学等技术应用日趋广泛,功能注释成为生命科学研究的中心任务,多组学整合分析成为全面解析生物学机理的主要手段。本专刊邀请了国内多组学领域的相关专家学者介绍了基因组学、转录组学、蛋白质组学及代谢组学等领域最新进展和应用成果,收录了相关文章28篇,以供从事多组学研究的科研工作者参考。     

整合转录组学数据的代谢网络研究进展

高通量测序技术的快速发展催生了涵盖各层次细胞生命活动的组学数据,如转录组学数据、蛋白质组学数据和互作组学数据等。同时,全基因组代谢网络模型在不断完善和增多。整合组学数据,对生物细胞的代谢网络进行更深入的模拟分析成为目前微生物系统生物学研究的热点。目前整合转录组学数据进行全基因组代谢网络分析的方法主要以流量平衡分析(FBA)为基础,通过辨识不同条件下基因表达的变化,进而优化目标函数以得到相应的流量分布或代谢模型。本文对整合转录组学数据的FBA分析方法进行总结和比较,并详细阐述了不同方法的优缺点,为分析特定问题选择合适的方法提供参考。     

整合分析多组学数据筛选疾病靶点的精准医学策略

随着高通量测序技术的不断发展与完善,对于不同层次和类型的生物组学数据的获取及分析方法也日趋成熟与完善。基于单组学数据的疾病研究已经发现了诸多新的疾病相关因子,而整合多组学数据研究疾病靶点的工作方兴未艾。生命体是一个复杂的调控系统,疾病的发生与发展涉及基因变异、表观遗传改变、基因表达异常以及信号通路紊乱等诸多层次的复杂调控机制,利用单一组学数据分析致病因子的局限性愈发显著。通过对多种层次和来源的高通量组学数据的整合分析,系统地研究临床发病机理、确定最佳疾病靶点已经成为精准医学研究的重要发展方向,将为疾病研究提供新的思路,并对疾病的早期诊断、个体化治疗和指导用药等提供新的理论依据。本文详细介绍了基因组、转录组和表观组等系统组学研究在疾病靶点筛选方面出现的新技术手段和研究进展,并对它们之间的整合分析新策略和优势进行了讨论。     

基于癌症基因组图谱计划多组学数据构建胶质母细胞瘤六基因预后模型

胶质母细胞瘤(glioblastoma,GBM)是最常见的原发性颅内肿瘤,恶性程度极高,患者预后极差.为了识别GBM预后生物标记物,建立预后模型,本研究通过分析癌症基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中GBM的表达谱数据,筛选出不同生存期GBM患者差异基因.利用GISTIC软...     

多组学分析在昆虫滞育中的应用

组学技术将生物的相关问题分别展现在基因、蛋白质和代谢物等不同层次水平上,已成为解读生命过程的重要工具。本文分别从转录组学、蛋白质组学、代谢组学以及组学间的联合应用等方面概括总结了组学技术在昆虫滞育研究中的应用情况,阐述了以转录组学、蛋白质组学和代谢组学为代表的多组学技术在昆虫滞育调控分子机制中取得的重要成果,并针对当前研究现状,对昆虫滞育中组学技术应用的前景和局限性进行了总结和展望,以期为昆虫滞育调控分子机制的研究提供参考依据。     

基于整合宏组学技术认识腐生生境功能微生物区系

微生物区系在天然生境中分布广泛,利用传统纯培养等方法无法全面认识其分布和功能,因此被认为是地球上的"暗物质"。随着新一代测序技术与高分辨率质谱技术的快速发展,研究者可以在非培养条件下全面快速分析天然生境中微生物组及其动态变化,这开启了微生物组时代,使得研究地球上"暗物质"成为可能,从而改变了微生物学研究的现状。腐生生境作为生物地球化学循环的重要推动部分,因其高效降解转化有机废弃物能力而被广泛关注。腐生生境由于原料多变、环境复杂等原因未能被全面深入研究,而整合宏组学技术则为解析相关生境微生物区系的多样性及其功能动态演替规律奠定了技术基础。基于整合宏组学数据分析与环境参数的优化,可以在认识微生物组及其功能的动态水平上,针对复杂物料建立高效降解转化的绿色转化工艺,促进农牧业废弃物无害化和资源化利用进程。     

黑曲霉组学研究进展

黑曲霉作为重要的工业发酵菌株,被广泛用于多种有机酸和工业用酶的生产。随着组学技术的日益发展和成熟,黑曲霉的基因组、转录组、蛋白质组、代谢组等组学数据不断增长,宣告着黑曲霉生物过程研究大数据时代的到来。从单一组学的数据分析、多组学的比较到以基因组代谢网络模型为中心的多组学整合研究,人们对黑曲霉高效生产机制的理解不断深入和系统,这为通过遗传改造和过程调控对菌株的生产性能进行理性的全局优化提供了可能。本文回顾和总结了近年来黑曲霉的组学研究进展,并提出黑曲霉组学研究未来的发展方向。     

多组学大数据共享平台研究进展

高通量检测技术的快速发展催生了海量的多组学数据，数据驱动型研究规模正逐步超越传统假设型研究。不同层次组学数据的组合，通过对系统生物学和疾病发展更深入和全面的解读，持续改变生物医学研究方式。同时，多组学数据庞大的数据规模、异质的数据特性，以及强烈的数据共享内源性需求，都推动组学数据向规模化、平台化、标准化共享的方向发展。该文首先介绍了代表性的多组学平台和各组学数据的特点，接着以多维组学数据百科全书NODE为例，从多组学数据融合和多组学数据安全共享两方面对相应的方法和技术进行了细致的阐述，并展望了多组学数据平台未来的发展方向。     

多组学助力紫杉醇合成生物学研究

紫杉醇是高效的天然抗癌产物,广泛用于多种癌症的临床治疗。目前紫杉醇的生产主要是从红豆杉属(Taxus)植物中提取天然前体(如巴卡亭Ⅲ)然后再化学合成。受制于红豆杉植物资源,导致制药成本高。合成生物学的兴起为紫杉醇原料药的获取提供了新途径,但紫杉醇合成生物学的研究还有待推进。近年来,多组学被逐步应用到紫杉醇的合成生物学研究中。本文综述了多组学助力紫杉醇合成通路基因、调控基因和异源合成研究的最新进展,为紫杉醇的合成生物学研究提供了新的见解。     

多组学技术及其在生命科学研究中应用概述

随着新一代测序技术、高分辨质谱技术、多组学整合分析方法及数据库的发展,组学技术正从传统的单一组学向多组学技术发展。以多组学驱动的系统生物学研究将带来生命科学研究的新范式。本文简要概述了基因组学、表观基因组学、转录组学,蛋白质组学及代谢组学的进展,重点介绍多组学技术平台的组成和功能,多组学技术的应用现状及在合成生物学及生物医学等领域的应用前景。     

玉米RFLP连锁图谱构建及大斑病QTL定位

玉米大斑病菌存在有生理小种分化的现象,目前5个已定名的生理小种在我国均已发现,还有一些尚未定位名的新类群也出出现,提高玉米对大斑病的抗性,只有提高数量抗性才能达到目的,为了弄清楚玉米对大斑病数量抗性的基因数目及效效应,利用抗病自交5系P138和感病自交系缩3为亲本构建了F2：3家系群体,采用RFLP标记构建了包含了124个标记的玉米RFLP连锁图,覆盖玉米基因组1999．8cM,标记间平均距离为16．5cM,定位了玉米大斑病的病斑长,病斑宽和病斑面积的QTL分别为3、3、2个,其联合贡献率分别为58．1％、71．5％和27．5％,没有检测到病斑数／叶的QTL,其表现为单基因或者寡基因控制的性状,研究结果增加了对玉米大斑病的认识,对玉米抗大斑病育种具有重要的指导意义。     

玉米SSR遗传图谱的构建及产量性状基因定位

利用中国农大培育的高产,多抗性玉米杂交组合农大3138的F2：3家系为材料,构建了具有80对SSR标记的玉米遗传图谱,标记间平均距离25．42,覆盖玉米基因组的2033.4cm,采用随机区组田间设计,考察了230个家系的穗长,秃尖长,穗粗,穗行数,千粒重,穗重,单株粒重,利用区间作图法分析了影响各性状的数量性状基因座位（QTL）,共检测到30个QTLs,单个性状的QTLs为3－5个,QTLs解释变异量占总变异量的比例变化范围为9．5％－55．3％。     

Piggy-BACing the Human Genome I: Constructing a Porcine BAC Physical Map Through Comparative Genomics

Availability of the human genome sequence and high similarity between humans and pigs at the molecular level provides an opportunity to use a comparative mapping approach to piggy-BAC the human genome. In order to advance the pig genome sequencing initiative, sequence similarity between large-scale porcine BAC-end sequences (BESs) and human genome sequence was used to construct a comparatively-anchored porcine physical map that is a first step towards sequencing the pig genome. A total of 50,300 porcine BAC clones were end-sequenced, yielding 76,906 BESs after trimming with an average read length of 538 bp. To anchor the porcine BACs on the human genome, these BESs were subjected to BLAST analysis using the human draft sequence, revealing 31.5% significant hits (E < e^?5). Both genic and non-genic regions of homology contributed to the alignments between the human and porcine genomes. Porcine BESs with unique homology matches within the human genome provided a source of markers spaced approximately 70 to 300 kb along each human chromosome. In order to evaluate the utility of piggy-BACing human genome sequences, and confirm predictions of orthology, 193 evenly spaced BESs with similarity to HSA3 and HSA21 were selected and then utilized for developing a high-resolution (1.22 Mb) comparative radiation hybrid map of SSC13 that represents a fusion of HSA3 and HSA21. Resulting RH mapping of SSC13 covers 99% and 97% of HSA3 and HSA21, respectively. Seven evolutionary conserved blocks were identified including six on HSA3 and a single syntenic block corresponding to HSA21. The strategy of piggy-BACing the human genome described in this study demonstrates that through a directed, targeted comparative genomics approach construction of a high-resolution anchored physical map of the pig genome can be achieved. This map supports the selection of BACs to construct a minimal tiling path for genome sequencing and targeted gap filling. Moreover, this approach is highly relevant to other genome sequencing projects.     

Transformative Network Modeling of Multi-omics Data Reveals Detailed Circuits,Key Regulators,and Potential Therapeutics for Alzheimer’s Disease

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玉米分子伴侣基因ZmBiP1的表达模式和功能研究

以抗旱玉米自交系旱21为材料,克隆获得玉米分子伴侣基因Zm Bi P1,通过荧光定量PCR技术研究Zm Bi P1基因的表达模式,并将Zm Bi P1基因转入拟南芥中研究其功能。荧光定量PCR结果表明,Zm Bi P1基因在玉米自交系旱21的不同组织器官中均有表达,且在子房中表达量最高。Zm Bi P1基因受甘露醇胁迫诱导上调表达,受盐胁迫诱导下调表达。转基因拟南芥功能验证结果表明,过表达Zm Bi P1基因导致拟南芥在种子萌发时期对盐和甘露醇胁迫的耐受能力减弱。这些结果表明Zm Bi P1基因可能是逆境反应信号传递途径的负调节因子。     

Using Integrative Modeling Platform to compute,validate, and archive a model of a protein complex structure

Biology is advanced by producing structural models of biological systems, such as protein complexes. Some systems are recalcitrant to traditional structure determination methods. In such cases, it may still be possible to produce useful models by integrative structure determination that depends on simultaneous use of multiple types of data. An ensemble of models that are sufficiently consistent with the data is produced by a structural sampling method guided by a data‐dependent scoring function. The variation in the ensemble of models quantified the uncertainty of the structure, generally resulting from the uncertainty in the input information and actual structural heterogeneity in the samples used to produce the data. Here, we describe how to generate, assess, and interpret ensembles of integrative structural models using our open source Integrative Modeling Platform program ( https://integrativemodeling.org ).     

Identification of a QTL in Mus musculus for Alcohol Preference,Withdrawal, and Ap3m2 Expression Using Integrative Functional Genomics and Precision Genetics

Extensive genetic and genomic studies of the relationship between alcohol drinking preference and withdrawal severity have been performed using animal models. Data from multiple such publications and public data resources have been incorporated in the GeneWeaver database with >60,000 gene sets including 285 alcohol withdrawal and preference-related gene sets. Among these are evidence for positional candidates regulating these behaviors in overlapping quantitative trait loci (QTL) mapped in distinct mouse populations. Combinatorial integration of functional genomics experimental results revealed a single QTL positional candidate gene in one of the loci common to both preference and withdrawal. Functional validation studies in Ap3m2 knockout mice confirmed these relationships. Genetic validation involves confirming the existence of segregating polymorphisms that could account for the phenotypic effect. By exploiting recent advances in mouse genotyping, sequence, epigenetics, and phylogeny resources, we confirmed that Ap3m2 resides in an appropriately segregating genomic region. We have demonstrated genetic and alcohol-induced regulation of Ap3m2 expression. Although sequence analysis revealed no polymorphisms in the Ap3m2-coding region that could account for all phenotypic differences, there are several upstream SNPs that could. We have identified one of these to be an H3K4me3 site that exhibits strain differences in methylation. Thus, by making cross-species functional genomics readily computable we identified a common QTL candidate for two related bio-behavioral processes via functional evidence and demonstrate sufficiency of the genetic locus as a source of variation underlying two traits.     

Isolation,Characterization and Functional Examination of the Gingival Immune Cell Network

Immune cell networks in tissues play a vital role in mediating local immunity and maintaining tissue homeostasis, yet little is known of the resident immune cell populations in the oral mucosa and gingiva. We have established a technique for the isolation and study of immune cells from murine gingival tissues, an area of constant microbial exposure and a vulnerable site to a common inflammatory disease, periodontitis. Our protocol allows for a detailed phenotypic characterization of the immune cell populations resident in the gingiva, even at steady state. Our procedure also yields sufficient cells with high viability for use in functional studies, such as the assessment of cytokine secretion ex vivo. This combination of phenotypic and functional characterization of the gingival immune cell network should aid towards investigating the mechanisms involved in oral immunity and periodontal homeostasis, but will also advance our understanding of the mechanisms involved in local immunopathology.     

Investigation and a New Evaluation Method of the Resistance of Maize Hybrids grown in Hungary to Fusarium moulds

Thirty maize hybrids grown in Hungary representing groups FAO 200–299, FAO 400–499 and FAO 500-were studied in order to obtain information about genotypic resistance to Fusarium moulds. The plants were grown on an experimental farm and were inoculated using the toothpick method with Fusarium graminearum and Fusarium culmorum . In addition maize grain meals were also inoculated with isolates of moulds. Measurements were made of the mould-covered surface area of the ears 9 weeks after inoculation and of the zearalenone and T2-toxin content of the inoculated maize meals. Large differences among hybrids were observed for the mould-covered area of the ear surface (2.00–38.88%), the zearalenone content (4.20–71.20 mg/kg) and the T2-toxin content (1.60–122.50 mg/kg). Relatively poor correlation ( r =0.489) was found between the area of mould covering the ear surface and mycotoxin content of maize. Bearing in mind that the user of feed grain is interested in obtaining a feed with the lowest mycotoxin content, a new method of evaluation of hybrids which uses a toxin–mould index (TMI) was introduced. This index is calculated on the basis of both growth rate of moulds and their toxin-producing activity. Although a decreasing tendency in resistance of hybrids with a longer growing vegetation period could be observed, resistant genotypes were found in every FAO group, confirming the views that in addition to the influence of duration of the vegetation period on the resistance, genetic factors may also play a significant role.