New software to detect horizontal gene transfer in microbiomes: from forage to the rumen

检测微生物组水平基因转移的新软件：从饲料到瘤胃

• 批准号: 2878898
• 金额: --
• 依托单位: Aberystwyth University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2878898
• 关键词: New; software; detect; horizontal; gene

HypothesisHorizontal gene transfer (HGT) is the sharing of genetic material between organisms that are not in a vertical relationship of inheritance i.e. between parents and offspring. HGT is widely recognized as a mechanism for evolutionary adaptation. While it is has been studied in bacteria and archaea for some time, it is also being seen of increasing importance for understanding eukaryotic evolution. Recent reviews of HGT emphasise the need to develop better computational methods to detect HGT, especially in eukaryotes. Approaches to detecting HGT events can be divided into two. The first involves the construction of phylogenetic trees using sequence alignment, to detect differences between the evolutionary history of a species and the evolutionary history of individual gene sequences. The second approach involves the analysis of properties intrinsic to genome sequences i.e. the patterns of order and disorder, repeats, codon usage biases, and k-mer content (k-mers are small oligonucleotides). These approaches are collectively known as alignment-free sequence analysis: Dr Swain has recently published a novel machine learning methodology that demonstrates how alignment-free methods can be improved through calibration using training data sets. We hypothesise that our novel process of calibrating alignment-free methods will give significant performance gains over existing approaches. The process of calibration indicates the optimal parameter set to use, and provides a probability score for the likelihood of detecting a true positive. Calibration can be performed in different ways, according to the sequence feature to be detected. These probabilities can then be amalgamated e.g. using Bayesian statistics, and combined with phylogeny analysis. This approach is superior to existing approaches because they estimate appropriate parameters, and cannot allocate probability scores. Our improved approach to HGT detection will generate novel insights into systems where HGT is hypothesised to play an important role. Typically HGTs occur between species that live in biological promiscuity, such as parasites, pathogens (including viruses), symbionts, and their hosts. Objectives1.To develop novel software for detecting horizontal gene transfer that can be applied to existing collections of diverse genome sequences. Demonstrate performance gains through comparison to other current approaches. 2.HGT is hypothesised to generate evolutionary adaptions that allow endophytes (prokaryotes) to enter a symbiotic relationship with their host plants, such as the acquisition of certain metabolic functions. We will apply our software to a unique Aberystwyth collection of approximately 100 endophyte genomes derived from grasses, to detect HGT events in these phenotypes. Endophyte genomes will be compared to their free-living or pathogenic relatives, and those found within the rumen, to better understand the role of HGT in developing their current genetic structure.3.Over fifteen years ago it was shown that ciliates (eukaryotes) in the rumen have acquired, through HGT from bacteria, 46 genes related to carbohydrate degradation. More recent data will enable a much deeper analysis of this important finding, using our software. In addition, we plan to expand our approach to explore horizontal transposable element transfer (HTT) in the ciliates. Ciliates are a model system for the study of the interaction between eukaryotic germlines and somatic lines, especially with regard to the invasion and defence against transposable elements.JustificationHGT and HTT are key processes that help organisms to adapt and generate new phenotypes, it is therefore important to improve our understanding of the roles it plays in ecological systems relating to agriculture. Better understanding of HGT will help monitor the spread of antimicrobial resistance throughout the agricultural system. Moreover, an improved understanding of HGT will provide insights into the development me

假设的基因转移（HGT）是生物之间遗传物质的共享，这些生物与遗传性不存在垂直关系，即父母和后代之间的垂直关系。 HGT被广泛认为是进化适应的机制。虽然已经在细菌和古细菌中进行了一段时间的研究，但人们也认为它对理解真核进化的重要性越来越重要。 HGT的最新评论强调需要开发更好的计算方法来检测HGT，尤其是在真核生物中。检测HGT事件的方法可以分为两个。首先涉及使用序列比对构建系统发育树，以检测物种的进化史与单个基因序列的进化史之间的差异。第二种方法涉及对基因组序列固有的特性分析，即有序和无序的模式，重复序列，密码子使用偏见和K-MER含量（K-MER是小寡核苷酸）。这些方法集体称为无对解的序列分析：Swain博士最近发表了一种新型的机器学习方法，该方法证明了如何使用培训数据集通过校准来改善无对齐方法。我们假设我们的新型校准无对准方法的新过程将使现有方法具有显着的性能提高。校准过程指示要使用的最佳参数集，并为检测真正阳性的可能性提供了概率分数。根据要检测到的序列特征，可以以不同的方式进行校准。然后可以将这些概率合并，例如使用贝叶斯统计，并与系统发育分析结合使用。这种方法优于现有方法，因为它们估计适当的参数，并且无法分配概率分数。我们改进的HGT检测方法将产生对HGT被假设起着重要作用的系统的新见解。通常，HGT发生在生活在生物滥交中的物种之间，例如寄生虫，病原体（包括病毒），共生体及其宿主。目标1.开发用于检测水平基因转移的新型软件，该软件可应用于现有的不同基因组序列的集合。通过与其他当前方法进行比较来展示性能提高。 2.假设HGT可以产生允许内生菌（原核生物）与宿主植物的共生关系的进化适应性，例如获得某些代谢功能。我们将把软件应用于大约100个源自草的内生菌基因组的独特的Aberystwyth集合，以检测这些表型中的HGT事件。内生菌基因组将与他们的自由生活或致病亲戚进行比较，以及在瘤胃中发现的亲戚，以更好地理解HGT在开发其当前遗传结构中的作用。3.15年前，在瘤胃中，蛋白糖（真核生物）在肿瘤中已通过细菌，与含碳纤维相关的46个基因获得的HGT中获得。最新的数据将使用我们的软件对这一重要发现进行更深入的分析。此外，我们计划扩展我们的方法，以探索纤毛中的水平转座元件转移（HTT）。纤毛是一个模型系统，用于研究真核细菌和躯体线之间的相互作用，尤其是在针对可替代元素的入侵和防御方面。JustificationHgt和HTT是帮助生物体适应和产生新表型的关键过程，因此，重要的是我们对IT在生态系统中的了解非常重要。更好地了解HGT将有助于监测抗菌素耐药性在整个农业系统中的传播。此外，对HGT的改进理解将为我提供见解