ABSTRACT
Synthetic lethality (SL) occurs when mutations in two genes together lead to cell or organism death, while a single mutation in either gene does not have a significant impact. This concept can also be extended to three or more genes for SL. Computational and experimental methods have been developed to predict and verify SL gene pairs, especially for yeast and Escherichia coli. However, there is currently a lack of a specialized platform to collect microbial SL gene pairs. Therefore, we designed a synthetic interaction database for microbial genetics that collects 13,313 SL and 2,994 Synthetic Rescue (SR) gene pairs that are reported in the literature, as well as 86,981 putative SL pairs got through homologous transfer method in 281 bacterial genomes. Our database website provides multiple functions such as search, browse, visualization, and Blast. Based on the SL interaction data in the S. cerevisiae, we review the issue of duplications' essentiality and observed that the duplicated genes and singletons have a similar ratio of being essential when we consider both individual and SL. The Microbial Synthetic Lethal and Rescue Database (Mslar) is expected to be a useful reference resource for researchers interested in the SL and SR genes of microorganisms. Mslar is open freely to everyone and available on the web at http://guolab.whu.edu.cn/Mslar/.
Subject(s)
Neoplasms , Saccharomyces cerevisiae , Humans , Saccharomyces cerevisiae/genetics , Synthetic Lethal Mutations , Mutation , Genome, Bacterial/genetics , Databases, Genetic , Neoplasms/geneticsABSTRACT
Proteins encoded by small open reading frames (sORFs) can serve as functional elements playing important roles in vivo. Such sORFs also constitute the potential pool for facilitating the de novo gene birth, driving evolutionary innovation and species diversity. Therefore, their theoretical and experimental identification has become a critical issue. Herein, we proposed a protein-coding sORFs prediction method merely based on integrative sequence-derived features. Our prediction performance is better or comparable compared with other nine prevalent methods, which shows that our method can provide a relatively reliable research tool for the prediction of protein-coding sORFs. Our method allows users to estimate the potential expression of a queried sORF, which has been demonstrated by the correlation analysis between our possibility estimation and codon adaption index (CAI). Based on the features that we used, we demonstrated that the sequence features of the protein-coding sORFs in the two domains have significant differences implying that it might be a relatively hard task in terms of cross-domain prediction, hence domain-specific models were developed, which allowed users to predict protein-coding sORFs both in eukaryotes and prokaryotes. Finally, a web-server was developed and provided to boost and facilitate the study of the related field, which is freely available at http://guolab.whu.edu.cn/codingCapacity/index.html.
Subject(s)
Random Forest , Open Reading Frames/geneticsABSTRACT
Synthetic biology is an important interdisciplinary field that has emerged in this century, focusing on the rewriting and reprogramming of DNA through the cycles of "design-edit", and so, the cell's own operating system, its genome, is naturally coming into focus. Here, we propose EcoliGD, an online genome design tool with a visual interactive interface and the function of browsing information, as well as the ability to perform insertion, exchange, deletion, and codon replacement operations on the E. coli genome and display the results in real-time. Users can utilize EcoliGD to check various functional characteristic about E. coli genes, to help them build their genomes. Furthermore, we also collected experimentally verified large genomic segments that have been successfully deleted from the genome for users to choose from and simplify the genome. EcoliGD can help recode the entire E. coli genome, providing a novel way to explore the diversity and function of this microorganism. The EcoliGD web tool is available at http://guolab.whu.edu.cn/EcoliGD/.