Evolutionary Bioinformatics最新文献

B12D-Like is a member of the B12D domain-containing protein family, which includes several transmembrane proteins in plants. In this study, the cDNA of PgB12D-Like from Pennisetum glaucum subsp. monodii (Maire) Brunken was sequenced and characterized. The 446-bp cDNA for PgB12D-Like encodes for a deduced protein of 95 amino acids. The PgB12D-Like protein contains a B12D domain and a transmembrane helix embedded in the mitochondrial membrane. Cis-regulatory elements analysis reveals binding sites for various transcription factors involved in responses to stress, light, and plant hormones in the putative promoter sequence for PgB12D-Like. Several proteins involved in floral organ development were also found to have binding sites in the PgB12D-Like promoter, such as agamous-like proteins and squamosa promoter binding proteins. Real-time PCR reveals high expression of PgB12D-Like in flowers during heading, whereas its expression in a 4-day-old seedling shoot was the lowest. Moreover, cold, drought, and heat stress were found to upregulate PgB12D-Like, whereas gibberellic acid downregulated its expression in seedlings. The present study helps to uncover the function of the B12D-Like in response to plant hormones and abiotic stress during P. glaucum development.

Lineage-specific genes can contribute to the emergence and evolution of novel traits and adaptations. Tardigrades are animals that have adapted to tolerate extreme conditions by undergoing a form of cryptobiosis called anhydrobiosis, a physical transformation to an inactive desiccated state. While studies to understand the genetics underlying the interspecies diversity in anhydrobiotic transitions have identified tardigrade-specific genes and family expansions involved in this process, the contributions of species-specific genes to the variation in tardigrade development and cryptobiosis are less clear. We used previously published transcriptomes throughout development and anhydrobiosis (5 embryonic stages, 7 juvenile stages, active adults, and tun adults) to assess the transcriptional biases of different classes of genes between 2 tardigrade species, Hypsibius exemplaris and Ramazzottius varieornatus. We also used the transcriptomes of 2 other tardigrades, Echiniscoides sigismundi and Richtersius coronifer, and data from 3 non-tardigrade species (Adenita vaga, Drosophila melanogaster, and Caenorhabditis elegans) to help identify lineage-specific genes. We found that lineage-specific genes have generally low and narrow expression but are enriched among biased genes in different stages of development depending on the species. Biased genes tend to be specific to early and late development, but there is little overlap in functional enrichment of biased genes between species. Gene expansions in the 2 tardigrades also involve families with different functions despite homologous genes being expressed during anhydrobiosis in both species. Our results demonstrate the interspecific variation in transcriptional contributions and biases of lineage-specific genes during development and anhydrobiosis in 2 tardigrades.

Background: Statistical methods developed to address various questions in single-cell datasets show increased variability to different parameter regimes. In order to delineate further the robustness of commonly utilized methods for single-cell RNA-Seq, we aimed to comprehensively review scRNA-Seq analysis workflows in the setting of dimension reduction, clustering, and trajectory inference.

Methods: We utilized datasets with temporal single-cell transcriptomics profiles from public repositories. Combining multiple methods at each level of the workflow, we have performed over 6k analysis and evaluated the results of clustering and pseudotime estimation using adjusted rand index and rank correlation metrics. We have further integrated neural network methods to assess whether models with increased complexity can show increased bias/variance trade-off.

Results: Combinatorial workflows showed that utilizing non-linear dimension reduction techniques such as t-SNE and UMAP are sensitive to initial preprocessing steps hence clustering results on dimension reduced space of single-cell datasets should be utilized carefully. Similarly, pseudotime estimation methods that depend on previous non-linear dimension reduction steps can result in highly variable trajectories. In contrast, methods that avoid non-linearity such as WOT can result in repeatable inferences of temporal gene expression dynamics. Furthermore, imputation methods do not improve clustering or trajectory inference results substantially in terms of repeatability. In contrast, the selection of the normalization method shows an increased effect on downstream analysis where ScTransform reduces variability overall.

SARS-CoV-2, responsible for the current COVID-19 pandemic that claimed over 5.0 million lives, belongs to a class of enveloped viruses that undergo quick evolutionary adjustments under selection pressure. Numerous variants have emerged in SARS-CoV-2, posing a serious challenge to the global vaccination effort and COVID-19 management. The evolutionary dynamics of this virus are only beginning to be explored. In this work, we have analysed 1.79 million spike glycoprotein sequences of SARS-CoV-2 and found that the virus is fine-tuning the spike with numerous amino acid insertions and deletions (indels). Indels seem to have a selective advantage as the proportions of sequences with indels steadily increased over time, currently at over 89%, with similar trends across countries/variants. There were as many as 420 unique indel positions and 447 unique combinations of indels. Despite their high frequency, indels resulted in only minimal alteration of N-glycosylation sites, including both gain and loss. As indels and point mutations are positively correlated and sequences with indels have significantly more point mutations, they have implications in the evolutionary dynamics of the SARS-CoV-2 spike glycoprotein.

Computationally annotating proteins with a molecular function is a difficult problem that is made even harder due to the limited amount of available labeled protein training data. Unsupervised protein embeddings partly circumvent this limitation by learning a universal protein representation from many unlabeled sequences. Such embeddings incorporate contextual information of amino acids, thereby modeling the underlying principles of protein sequences insensitive to the context of species. We used an existing pre-trained protein embedding method and subjected its molecular function prediction performance to detailed characterization, first to advance the understanding of protein language models, and second to determine areas of improvement. Then, we applied the model in a transfer learning task by training a function predictor based on the embeddings of annotated protein sequences of one training species and making predictions on the proteins of several test species with varying evolutionary distance. We show that this approach successfully generalizes knowledge about protein function from one eukaryotic species to various other species, outperforming both an alignment-based and a supervised-learning-based baseline. This implies that such a method could be effective for molecular function prediction in inadequately annotated species from understudied taxonomic kingdoms.

Background: Sepsis is a dysregulated host response to pathogens. Delay in sepsis diagnosis has become a primary cause of patient death. This study determines some factors to prevent septic shock in its early stage, contributing to the early treatment of sepsis.

Methods: The sequencing data (RNA- and miRNA-sequencing) of patients with septic shock were obtained from the NCBI GEO database. After re-annotation, we obtained lncRNAs, miRNA, and mRNA information. Then, we evaluated the immune characteristics of the sample based on the ssGSEA algorithm. We used the WGCNA algorithm to obtain genes significantly related to immunity and screen for important related factors by constructing a ceRNA regulatory network.

Result: After re-annotation, we obtained 1708 lncRNAs, 129 miRNAs, and 17 326 mRNAs. Also, through the ssGSEA algorithm, we obtained 5 important immune cells. Finally, we constructed a ceRNA regulation network associated with SS pathways.

Conclusion: We identified 5 immune cells with significant changes in the early stage of septic shock. We also constructed a ceRNA network, which will help us explore the pathogenesis of septic shock.

The Aurora kinases form a family of 3 genes encoding serine/threonine kinases and are involved in the regulation of cell division during the mitosis. This study was designed to investigate the prognostic role of Aurora kinases in hepatocellular carcinoma (HCC). In this study, we analyzed the expression, overall survival (OS) data, promoter methylation level, and relationship with immunoinhibitors of Aurora kinases in patients with HCC from GEPIA2, UALCAN, OncoLnc, and TISIDB databases. Protein-protein interaction (PPI) network, gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analysis were performed using the STRING database and Cytoscape software. We found that the mRNA expression, stages of HCC, and OS of AURKA and AURKB in HCC tissues were significantly different from control tissues, but there were significant inconsistencies in promoter methylation level and relationship with immunoinhibitors for AURKA and AURKB. None of the above items were significantly different for AURKC. Furthermore, a hub module including AURKA, AURKB, and AURKC was identified within the PPI network constructed with the Molecular Complex Detection (MCODE) plug-in in Cytoscape software. Our results show that AURKB could be a potential biomarker for HCC prognosis.

The microbiome plays diverse roles in many diseases and can potentially contribute to cancer development. Breast cancer is the most commonly diagnosed cancer in women worldwide. Thus, we investigated whether the gut microbiota differs between patients with breast carcinoma and those with benign tumors. The DNA of the fecal microbiota community was detected by Illumina sequencing and the taxonomy of 16S rRNA genes. The α-diversity and β-diversity analyses were used to determine richness and evenness of the gut microbiota. Gene function prediction of the microbiota in patients with benign and malignant carcinoma was performed using PICRUSt. There was no significant difference in the α-diversity between patients with benign and malignant tumors (P = 3.15e^-1 for the Chao index and P = 3.1e^-1 for the ACE index). The microbiota composition was different between the 2 groups, although no statistical difference was observed in β-diversity. Of the 31 different genera compared between the 2 groups, level of only Citrobacter was significantly higher in the malignant tumor group than that in benign tumor group. The metabolic pathways of the gut microbiome in the malignant tumor group were significantly different from those in benign tumor group. Furthermore, the study establishes the distinct richness of the gut microbiome in patients with breast cancer with different clinicopathological factors, including ER, PR, Ki-67 level, Her2 status, and tumor grade. These findings suggest that the gut microbiome may be useful for the diagnosis and treatment of malignant breast carcinoma.

We aimed to discover prognostic factors of muscle-invasive bladder cancer (MIBC) and investigate their relationship with immune therapies. Online data of MIBC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) database. Weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis were applied to classify genes into different groups. Venn diagram was used to find the intersection of genes, and prognostic efficacy was proved by Kaplan-Meier analysis. Heatmap was utilized for differential analysis. Riskscore (RS) was calculated according to multivariate Cox analysis and evaluated by receiver operating characteristic curve (ROC). MIBC samples from TCGA and GEO were analyzed by WGCNA and univariate Cox analysis and intersected at 4 genes, CLK4, DEDD2, ENO1, and SYTL1. Higher SYTL1 and DEDD2 expressions were significantly correlated with high tumor grades. Riskscore based on genes showed great prognostic efficiency in predicting overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in TCGA dataset (P < .001). The area under the ROC curve (AUC) of RS reached 0.671 in predicting 1-year survival and 0.653 in 3-year survival. KEGG pathways enrichment filtered 5 enriched pathways. xCell analysis showed increased T cell CD4+ Th2 cell, macrophage, macrophage M1, and macrophage M2 infiltration in high RS samples (P < .001). In immune checkpoints analysis, PD-L1 expression was significantly higher in patients with high RS. We have, therefore, constructed RS as a convincing prognostic index for MIBC patients and found potential targeted pathways.