Motivation: Protein-to-genome alignment is critical to annotating genes in non-model organisms. While there are a few tools for this purpose, all of them were developed over ten years ago and did not incorporate the latest advances in alignment algorithms. They are inefficient and could not keep up with the rapid production of new genomes and quickly growing protein databases.
Results: Here we describe miniprot, a new aligner for mapping protein sequences to a complete genome. Miniprot integrates recent techniques such as k-mer sketch and SIMD-based dynamic programming. It is tens of times faster than existing tools while achieving comparable accuracy on real data.
Availability and implementation: https://github.com/lh3/miniprot
Replication of SARS-CoV2 virions is an error-prone process which may eventually generate a percentage of impaired protein copies with complete lack of functionality. For instance, after RNA mis-replication, a very premature stop codon (UAG, UAA, UGA) coding for a prematurely truncated (nonsense-mutated) spike protein may occur. In the natural virus replication process via cell infection, the nonsense genomes are corrected by the proofreading enzymes of the virus, strongly penalized by natural selection and condemned to a very short life by the host cell's mRNA watching mechanisms. However, for…
As the infection of 2019-nCoV coronavirus is quickly developing into a global pneumonia epidemic, careful analysis of its transmission and cellular mechanisms is sorely needed. In this report, we re-analyzed the computational approaches and findings presented in two recent manuscripts by Ji et al. (https://doi.org/10.1002/jmv.25682) and by Pradhan et al. (https://doi.org/10.1101/2020.01.30.927871), which concluded that snakes are the intermediate hosts of 2019-nCoV and that the 2019-nCoV spike protein insertions shared a unique similarity to HIV-1. Results from our re-implementation of the ana…
Bacterial genomes have been shown to be partitioned into several kilobases long chromosomal domains that are topologically independent from each other, meaning that change of DNA superhelicity in one domain does not propagate to neighbors. Both in vivo and in vitro experiments have been performed to question the nature of the topological barriers at play, leading to several predictions on possible molecular actors. Here, we address the question of topological barriers using polymer models of supercoiled DNA chains. More specifically, we determine under which conditions DNA-bridging proteins ma…
Increasing biological complexity is positively correlated with the relative genome-wide expansion of non-protein-coding DNA sequences
背景资料:在当前的基因组时代之前,有人认为生物体所使用的蛋白质编码基因的数量是衡量其复杂性的有效指标。然而,现在很清楚的是,主要的不一致性存在,生物复杂性和蛋白质编码基因的数量之间只有微弱的关系。例如,使用蛋白质编码基因数量作为评估生物复杂性的基础,将使尾索动物和昆虫的复杂性低于线虫,而人类的复杂性低于水稻。结果如下:我们分析了85个测序物种的非编码基因组DNA与总基因组DNA的比率(ncDNA/tgDNA),发现这个比率与生物学复杂性的增加密切相关。对于原核生物,ncDNA/tgDNA比率通常包含在0.05-0.24的带宽内,但在单细胞真核生物中上升到0.26-0.52,并且对于发育复杂的多细胞生物体上升到0.62-0.985。值得注意的是,原核生物物种的物种分布不均匀,接近平均值0.1177 ncDNA/tgDNA(p=1.58 x 10^-13),ncDNA/tgDNA与基因组大小呈非线性关系(r=0.15)。重要的是,ncDNA/tgDNA比率校正倍性,并且基本上不受重复序列的可变负荷的影响。结论:我们认为,所观察到的非编码DNA的增加和组成模式主要是增加的信息含量的函数。因此,内含子、基因间序列、重复元件和基因组DNA可能对复杂生物的进化和功能库比以前认识到的要重要得多。
Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2500 coronaviruses and computed >100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the 3 and 5 prime ends are the most structured elements in the viral genome and the 5 prime end has the strongest propensity to associate with human proteins. The domain encompassing nucleotides 23000-24000 is highly conserved both at the sequence and structural level, while the region upstream varies significantly. Th…