Identifying essential genes in a given organism is important for research on their fundamental roles in organism survival. Furthermore, if possible, uncovering the links between core functions or pathways with these essential genes will further help us obtain deep insight into the key roles of these genes. In this study, we investigated the essential and non-essential genes reported in a previous study and extracted gene ontology (GO) terms and biological pathways that are important for the determination of essential genes. Through the enrichment theory of GO and KEGG pathways, we encoded each essential/non-essential gene into a vector in which each component represented the relationship between the gene and one GO term or KEGG pathway. To analyze these relationships, the maximum relevance minimum redundancy (mRMR) was adopted. Then, the incremental feature selection (IFS) and support vector machine (SVM) were employed to extract important GO terms and KEGG pathways. A prediction model was built simultaneously using the extracted GO terms and KEGG pathways, which yielded nearly perfect performance, with a Matthews correlation coefficient of 0.951, for distinguishing essential and non-essential genes. To fully investigate the key factors influencing the fundamental roles of essential genes, the 21 most important GO terms and three KEGG pathways were analyzed in detail. In addition, several genes was provided in this study, which were predicted to be essential genes by our prediction model. We suggest that this study provides more functional and pathway information on the essential genes and provides a new way to investigate related problems.
1 February 2017 in Artificial Intelligence in Medicine
The CRISPR/Cas9 system is a creative and innovative gene editing biotechnology tool in genetic engineering. Although several achievements have been attained using the CRISPR/Cas9 system, it is still a challenge to avoid off-target effects and improve the editing efficacy. Previous efforts on evaluating the efficacy and designing the guide RNA mainly focused on DNA properties. However, some DNA features have not been characterized but can be reflected by protein properties such as the disorder features and the sequence conservation. In this study, we provided a computational framework to identify important features related to the efficacy of CRISPR/Cas9 focusing on the properties of the proteins encoded by the target DNA fragments. The feature selection method, maximal-relevance-minimal-redundancy (mRMR), was adopted to analyze these features. And incremental feature selection (IFS) together with support vector machine, were employed to extract optimal features, on which an optimal classifier can be constructed. As a result, 152 important features were extracted, with which an optimal classifier based on support vector machine was built. This classifier obtained the highest MCC value of 0.355. Finally, a series of detailed biological analyses were performed on the optimal features. From the results, we found that some key factors may differentially affect the binding activity of sgRNAs to their targets. Among them, the disorder status of the target protein sequences was found to be a major factor that is related to the efficacy of sgRNAs, suggesting the DNA features associated with the protein disorder status could also affect the CRISPR/Cas9 efficacy.