Deciphering overlapping regulatory signals in viral transcripts

该项目的主要目标是为病毒转录本中存在的重叠调控信号提供一个全面的计算概述，这对病毒复制周期的所有阶段都至关重要。它们中的许多与细胞生物中使用的信号明显不同，并且是由病毒的特定分类特异性生物学特征决定的。具体来说，病毒进化为入侵宿主免疫系统并利用其细胞内资源。它们也经过广泛的选择以提高复制效率。此外，它们需要能够在极端压力下（由于病毒入侵）的细胞中复制，从而在极其不寻常的细胞内环境中复制。由于这些原因，病毒倾向于利用细胞有机体中非常罕见（甚至不存在）的非规范调节过程。因此，我们预计不同的病毒组将采用不同的信号作为其复制策略的一部分，毫无疑问，许多（如果不是大多数的话）此类代码仍有待发现。该项目的具体科学目标如下：-开发一套算法，用于检测核苷酸/密码子组成异常模式的转录区域。这包括诸如密码子和密码子对偏倚、沿着转录物的不同折叠强度、rna和蛋白质的潜在结合位点、代表性过强和代表性不足的序列基序、在所有相关的病毒基因组数据集中进行重叠功能代码的大规模发现-提供结果的生物学解释并建立理论模型，解释发现的信号与mRNA翻译动力学和共翻译蛋白质折叠的相关性。该项目的具体技术目标如下：-开发用于检测和解释病毒转录本中功能信息的软件管道。-生成具有相关预测的可公开访问的数据库。项目过程中发现的所有调控信号将根据病毒类型、信号位置和预测功能进行组织。将提供不同病毒之间的比较分析设施。该数据库将使该领域的研究人员能够进一步研究和验证我们的预测。我们预期这项研究将对基础研究和应用研究产生重要影响。这将有助于更好地理解作用于病毒转录本的进化限制，也将为开发新型疫苗和抗病毒疗法提供有价值的信息。

The main goal of the project is to provide a comprehensive computational overview of the overlapping regulatory signals present in viral transcripts, which are crucial for all stages of the viral replication cycle. Many of them are distinctly different from the signals used in the cellular organisms and are dictated by the specific, taxonomy-specific biological features of viruses. Specifically, viruses evolve to invade the host immune system and exploit its intracellular resources. They also undergo extensive selection for replication efficiency. Furthermore, they need to be able to replicate in the cells that are under extreme stress (due to the virus invasion) and thus in extremely unusual intracellular environment. For these reasons viruses tend to exploit non-canonical regulatory processes that are very rare (or even do not exist) in cellular organisms. We therefore expect that different virus groups will employ different signals as part of their replication strategy, and there is no doubt that many, if not the majority, of such codes remain yet to be discovered.The specific scientific objectives of the project are as follows:- Develop a set of algorithms for detecting transcript regions with unusual patterns of nucleotide/codon composition. This includes features such as codon and codon pair bias, varying folding strength along the transcript, potential binding sites for RNAs and proteins, over- and under-represented sequence motifs, as well as the features pertinent to the decoding rate- Conduct a large-scale discovery of overlapping functional codes in all relevant viral genomic datasets- Provide a biological interpretation of the results and build theoretical models explaining the relevance of the discovered signals for the dynamics of mRNA translation and for co-translational protein foldingThe specific technical objectives of the project are as follows: - Develop a software pipeline for detecting and interpreting functional information in the viral transcripts.- Generate a publicly accessible database with the relevant predictions. All the regulatory signals discovered in the course of the project will be organized according to the virus type, signal location, and predicted functionality. Facilities for comparative analysis between different viruses will be provided. The database will enable researchers in the field to further study and validate our predictions.We anticipate that the proposed study will have important implications for both basic and applied research. It will help to better understand the evolutionary constraints acting on viral transcripts and will also provide valuable information for developing novel vaccines and anti-viral therapies.