ConProject-001

研究最充分的RNA分子结构，特别是tRNA和rRNA，以单一的优势构象存在。 然而，已知越来越多的小的非编码RNA序列通过在 多种稳定配置。预计这样的多模式结构主题点缀着 像基孔肯雅这样的RNA病毒基因组的低能结构，调节病毒的生命周期。刻画 这些小的重叠的稳定碱基对集合，嵌入到具有高度结构多样性的长序列中，是 对于理解关键结构信号如何编码这些重要病原体的功能至关重要。 这种协作利用了以前结果的互补优势-从 结构集合(轮廓分析)和下一代化学足迹(SHAPE-MAP)-应对挑战 在由三个甲型病毒基因组组成的测试集中发现多模式基序。这第一个目标将通过以下方式实现 制定必要的地貌轮廓特征和形状地图特征以识别目标 具有多种天然构象的区域。这些单独的结果将在单独的序列中由 在当前预测得到实验证实后，形状定向剖析的组合 方法论。第二个目标将展示对这些新主题的进化支持，首先跨越三个主题 测试序列，然后是整个字母病毒家族，通过计算代数的新应用 拓扑学。持久同调和单纯复形将被用来分析不同 生物信息在RNA病毒基因组中编码的范围，从基因组序列到 脊椎动物宿主。随后将对另外三个甲型病毒序列进行化学探测确认。 这个项目将通过整合新的数学模型和分析来扩展RNA折叠的前沿 基于组合学和代数拓扑学与化学足迹生物化学的最新进展 目的是为了在长RNA病毒基因组中识别具有多峰结构的重要基序。这个 本研究的结果是，甲型病毒基因组中一组新的二级结构基序是理想的候选者 作为重要功能元件的进一步研究，将是RNA病毒学家的重要资源。此外， 建议的理论和算法发展一般适用于所有RNA病毒，因此 给科学界带来了重大的效用和兴趣。

The most well-studied RNA molecular structures, notably tRNA and rRNA, exist as a single dominant conformation. However, a growing number of small non-coding RNA sequences are known to function by switching between multiple stable configurations. It is expected that such multi modal structural motifs punctuate the ensemble of low-energy structures for an RNA viral genome like Chikungunya, regulating the viral lifecycle. Characterizing these small overlapping sets of stable base pairs, embedded in lengthy sequences with high structural diversity, is essential to understanding how critical structural signals encode the functionality of these important pathogens. This collaboration leverages complementary strengths of previous results --- mining competing signals from the structural ensemble (profiling) and next generation chemical footprinting (SHAPE-MaP) --- to tackle the challenge of multi modal motif discovery in a test set of three alphavirus genomes. This first aim will be achieved by developing the necessary characterizations of profiling landscapes and of SHAPE-MaP signatures to identify target regions with multiple native conformations. These separate results will be validated in individual sequences by the combination of SHAPE-directed profiling, following experimental confirmation of the current prediction methodology. The second aim will demonstrate evolutionary support for these new motifs, first across the three test sequences and then the entire alphaviral family, through a new application of computational algebraic topology. Persistent homology and simplicial complexes will be used to analyze evolution across the different scales at which biological information is encoded in RNA viral genomes, ranging from genomic sequence to vertebrate host. This will be followed by chemical probing confirmation for three additional alphavirus sequences. This project will extend the frontiers of RNA folding by integrating new mathematical models and analyses based on combinatorics and algebraic topology with recent advances in the biochemistry of chemical footprinting for the purposes of identifying significant motifs with multimodal structure in lengthy RNA viral genomes. The results of this study, a set of novel secondary structure motifs in alphavirus genomes which are ideal candidates for further investigation as important functional elements, will be a key resource for RNA virologists. Furthermore, the proposed theoretical and algorithmic developments are generally applicable to all RNA viruses, and hence of significant utility and interest to the scientific community.