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A novel method for identifying key genes in macroevolution based on deep learning with attention mechanism.

ABSTRACT: Macroevolution can be regarded as the result of evolutionary changes of synergistically acting genes. Unfortunately, the importance of these genes in macroevolution is difficult to assess and hence the identification of macroevolutionary key genes is a major challenge in evolutionary biology. In this study, we designed various word embedding libraries of natural language processing (NLP) considering the multiple mechanisms of evolutionary genomics. A novel method (IKGM) based on three types of attention mechanisms (domain attention, kmer attention and fused attention) were proposed to calculate the weights of different genes in macroevolution. Taking 34 species of diurnal butterflies and nocturnal moths in Lepidoptera as an example, we identified a few of key genes with high weights, which annotated to the functions of circadian rhythms, sensory organs, as well as behavioral habits etc. This study not only provides a novel method to identify the key genes of macroevolution at the genomic level, but also helps us to understand the microevolution mechanisms of diurnal butterflies and nocturnal moths in Lepidoptera.

SUBMITTER: Mao J

PROVIDER: S-EPMC10643560 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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A novel method for identifying key genes in macroevolution based on deep learning with attention mechanism.

Mao Jiawei J Cao Yong Y Zhang Yan Y Huang Biaosheng B Zhao Youjie Y

Scientific reports 20231113 1

Macroevolution can be regarded as the result of evolutionary changes of synergistically acting genes. Unfortunately, the importance of these genes in macroevolution is difficult to assess and hence the identification of macroevolutionary key genes is a major challenge in evolutionary biology. In this study, we designed various word embedding libraries of natural language processing (NLP) considering the multiple mechanisms of evolutionary genomics. A novel method (IKGM) based on three types of a ...[more]

PMID: 37957311

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Project description:Phages, the natural predators of bacteria, were discovered more than 100 years ago. However, increasing antimicrobial resistance rates have revitalized phage research. Methods that are more time-consuming and efficient than wet-laboratory experiments are needed to help screen phages quickly for therapeutic use. Traditional computational methods usually ignore the fact that phage-bacteria interactions are achieved by key genes and proteins. Methods for intraspecific prediction are rare since almost all existing methods consider only interactions at the species and genus levels. Moreover, most strains in existing databases contain only partial genome information because whole-genome information for species is difficult to obtain. Here, we propose a new approach for interaction prediction by constructing new features from key genes and proteins via the application of K-means sampling to select high-quality negative samples for prediction. Finally, we develop DeepPBI-KG, a corresponding prediction tool based on feature selection and a deep neural network. The results show that the average area under the curve for prediction reached 0.93 for each strain, and the overall AUC and area under the precision-recall curve reached 0.89 and 0.92, respectively, on the independent test set; these values are greater than those of other existing prediction tools. The forward and reverse validation results indicate that key genes and key proteins regulate and influence the interaction, which supports the reliability of the model. In addition, intraspecific prediction experiments based on Klebsiella pneumoniae data demonstrate the potential applicability of DeepPBI-KG for intraspecific prediction. In summary, the feature engineering and interaction prediction approaches proposed in this study can effectively improve the robustness and stability of interaction prediction, can achieve high generalizability, and may provide new directions and insights for rapid phage screening for therapy.

Project description:BackgroundPeriodontitis is a chronic immuno-inflammatory disease characterized by inflammatory destruction of tooth-supporting tissues. Its pathogenesis involves a dysregulated local host immune response that is ineffective in combating microbial challenges. An integrated investigation of genes involved in mediating immune response suppression in periodontitis, based on multiple studies, can reveal genes pivotal to periodontitis pathogenesis. Here, we aimed to apply a deep learning (DL)-based autoencoder (AE) for predicting immunosuppression genes involved in periodontitis by integrating multiples omics datasets.MethodsTwo periodontitis-related GEO transcriptomic datasets (GSE16134 and GSE10334) and immunosuppression genes identified from DisGeNET and HisgAtlas were included. Immunosuppression genes related to periodontitis in GSE16134 were used as input to build an AE, to identify the top disease-representative immunosuppression gene features. Using K-means clustering and ANOVA, immune subtype labels were assigned to disease samples and a support vector machine (SVM) classifier was constructed. This classifier was applied to a validation set (Immunosuppression genes related to periodontitis in GSE10334) for predicting sample labels, evaluating the accuracy of the AE. In addition, differentially expressed genes (DEGs), signaling pathways, and transcription factors (TFs) involved in immunosuppression and periodontitis were determined with an array of bioinformatics analysis. Shared DEGs common to DEGs differentiating periodontitis from controls and those differentiating the immune subtypes were considered as the key immunosuppression genes in periodontitis.ResultsWe produced representative molecular features and identified two immune subtypes in periodontitis using an AE. Two subtypes were also predicted in the validation set with the SVM classifier. Three "master" immunosuppression genes, PECAM1, FCGR3A, and FOS were identified as candidates pivotal to immunosuppressive mechanisms in periodontitis. Six transcription factors, NFKB1, FOS, JUN, HIF1A, STAT5B, and STAT4, were identified as central to the TFs-DEGs interaction network. The two immune subtypes were distinct in terms of their regulating pathways.ConclusionThis study applied a DL-based AE for the first time to identify immune subtypes of periodontitis and pivotal immunosuppression genes that discriminated periodontitis from the healthy. Key signaling pathways and TF-target DEGs that putatively mediate immune suppression in periodontitis were identified. PECAM1, FCGR3A, and FOS emerged as high-value biomarkers and candidate therapeutic targets for periodontitis.

Dataset Information

A novel method for identifying key genes in macroevolution based on deep learning with attention mechanism.

Publications

A novel method for identifying key genes in macroevolution based on deep learning with attention mechanism.

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