An all-in-one web server for RNA structure prediction using evolutionary information

一种使用进化信息预测 RNA 结构的一体化网络服务器

• 批准号: 10574944
• 负责人: Elena Rivas
• 金额: $ 24.99万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10574944
• 关键词: Adopted; Adoption; Algorithms; Biological; Biology; Cells; Communities; Computational Biology; Computer software; Computing Methodologies; Development; Evaluation; Evolution; Experimental Designs; Family; Free Energy; Genome; Goals; Homologous Gene; Knowledge; Link; Maps; Methods; Modeling; Organism; Outcome; Output; Phylogenetic Analysis; RNA; RNA Sequences; Research; Retrieval; Running; Science; Sequence Alignment; Sequence Homologs; Site-Directed Mutagenesis; Sorting; Structure; Techniques; Technology; Time; Validation; Variant; Work; comparative; computerized tools; cost; improved; interest; novel; prediction algorithm; predictive tools; programs; protein structure prediction; structural biology; therapeutic RNA; tool; transcriptome; wasting; web platform; web server

Project Abstract RNA structure and function are intimately linked. To sort out what the myriad RNAs in transcriptomes are doing, we need rigorous approaches that also infer structure. Many predictive algorithms already exist, but they output models for any and every sequence, and different approaches often output different models for the same sequence. This results in suboptimal models that permeate the field, and in ascribing structure to RNAs that don't in fact have any conserved structure. What the field of RNA research needs now to go forward is a computational tool that will evaluate the likelihood that a certain RNA sequence has a biological structure, and propose that structure with the highest accuracy. The best approach to this issue has been for a long time the comparison of homologous sequences from diverse organisms. This same approach is actually at the basis of the most successful protein structure prediction tools. But a hindrance in the wide adoption of such approaches for predicting RNA structure is that sequence comparison requires knowledge and expertise in computational and structural biology as well as access to tools that are not mainstream. This proposal is about the development of a freely available webserver for reliably predicting RNA secondary and eventually tertiary structures using evolutionary information. This webserver will operate behind the scenes as a suite of tools (the outputs of which will be available for interested users), from homologous sequences retrieval to evaluation of the resulting model. First, this tool will automatically retrieve and align homologous sequences using existing and novel algorithms. This aim will search for relevant homologs to any single sequence entered as input, which represents an unmet challenge for most current programs. Second, the application using covariation analysis will address the likeliness that the input RNA sequence has a conserved structure, so not every sequence used as input will necessarily output a structure model. Subsequent modules in the online tool will evaluate the quality of the alignment, and possibly improve this alignment, so that a model with a confidence score could be proposed. Regardless of the outcome, the user will have a result that will take into account evolutionary as well as up-to-date RNA structural information, so it will not be biased by the use of a single set of parameters, as is often the case with existing predictive methods. A more holistic and straightforward computational tool harnessing evolutionary information will help disseminate the use of those methods to the larger RNA biology community, for maximum impact on experimental design in RNA research.

项目摘要 RNA结构和功能密切相关。弄清楚转录组中的众多RNA是什么 这样做，我们需要严格的方法来推断结构。许多预测算法已经存在，但是它们 每个序列的输出模型以及不同的方法通常会输出不同的模型 相同的序列。这导致次优模型渗透到田间，并将结构归因于RNA 实际上没有任何保守的结构。 RNA研究领域现在需要的是一个 计算工具将评估某个RNA序列具有生物结构的可能性，并且 提出该结构的精度最高。解决这个问题的最佳方法是很长一段时间以来 比较来自不同生物体的同源序列。同样的方法实际上是在 最成功的蛋白质结构预测工具。但是，这种方法广泛采用 用于预测RNA结构的是，序列比较需要计算方面的知识和专业知识 以及结构生物学以及获得不是主流的工具。该建议是关于 开发免费的网络服务器，以可靠地预测RNA次要的第三级 使用进化信息的结构。该Web服务器将以一套工具的套件在幕后运行（ 从同源序列检索到评估，其输出将适用于感兴趣的用户） 最终的模型。首先，此工具将使用 现有和新颖的算法。此目标将搜索与输入的任何单个序列相关的同源物 输入，这代表了大多数当前程序的挑战。第二，使用 协方差分析将解决输入RNA序列具有保守结构的可能性， 因此，并非每个用作输入的序列都必须输出结构模型。随后的模块 在线工具将评估对齐方式的质量，并可能改善这种对齐方式，以便模型 可以提出置信度得分。无论结果如何，用户都会有一个结果 考虑到进化以及最新的RNA结构信息，因此不会因使用而偏见 一组参数，与现有的预测方法相同。一个更整体的 直接的计算工具利用进化信息将有助于传播这些信息 较大的RNA生物学界的方法，以最大程度地影响RNA研究中的实验设计。