Bioinformatics

Most noncoding RNAs are considered by their expression at low levels and as having a limited phylogenetic distribution in the cytoplasm, indicating that they may be only involved in specific biological processes. However, recent studies showed the protein-coding potential of ncRNAs, indicating that they might be a source of some special proteins. Although there are increasing noncoding RNAs identified to be able to code proteins, it is challenging to distinguish coding RNAs from previously annotated ncRNAs, and to detect the proteins from their translation. In this article, we designed a pipeline to identify these noncoding RNAs in Arabidopsis thaliana from three NCBI GEO data sets with coding potential and predict their translation products. 31 311 noncoding RNAs were predicted to be translated into peptides, and they showed lower conservation rate than common proteins. In addition, we built an interaction network between these peptides and annotated Arabidopsis proteins using BIPS...

Identification of epistasis loci underlying rice flowering time by controlling population stratification and polygenic effect Additionally, reference 69 in the sentence "It is well known that protein ubiquitination alter their cellular location, affect their activity and promote or prevent protein interactions." has been removed. Both corrections have been made online and in print.

Statistical data-mining (DM) and machine learning (ML) are promising tools to assist in the analysis of complex dataset. In recent decades, in the precision of agricultural development, plant phenomics study is crucial for high-throughput phenotyping of local crop cultivars. Therefore, integrated or a new analytical approach is needed to deal with these phenomics data. We proposed a statistical framework for the analysis of phenomics data by integrating DM and ML methods. The most popular supervised ML methods; Linear Discriminant Analysis (LDA), Random Forest (RF), Support Vector Machine with linear (SVM-l) and radial basis (SVM-r) kernel are used for classification/prediction plant status (stress/non-stress) to validate our proposed approach. Several simulated and real plant phenotype datasets were analyzed. The results described the significant contribution of the features (selected by our proposed approach) throughout the analysis. In this study, we showed that the proposed appr...

RNA interference (RNAi) plays key roles in post-transcriptional and chromatin modification levels as well as regulates various eukaryotic gene expressions which involved in stress responses, development and maintenance of genome integrity during developmental stages. The whole mechanism of RNAi pathway is directly involved with the gene-silencing process by the interaction of Dicer-Like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) gene families. However, the genes of these three RNAi families are largely unknown yet in sweet orange (Citrus sinensis), though it is an economically important fruit plant all over the world. Therefore, a comprehensive investigation for genome-wide identification, characterization and diversity analysis of RNA silencing genes in C. sinensis was conducted and identified 4 CsDCL, 8 CsAGO and 4 CsRDR as RNAi genes. To characterize and validate the predicted genes of RNAi families, various bioinformatics analysis was conducted. Phylogenetic a...

Outbreaks of COVID-19 caused by the novel coronavirus SARS-CoV-2 is still a threat to global human health. In order to understand the biology of SARS-CoV-2 and developing drug against COVID-19, a vast amount of genomic, proteomic, interatomic, and clinical data is being generated, and the bioinformatics researchers produced databases, webservers and tools to gather those publicly available data and provide an opportunity of analyzing such data. However, these bioinformatics resources are scattered and researchers need to find them from different resources discretely. To facilitate researchers in finding the resources in one frame, we have developed an integrated web portal called OverCOVID (http://bis.zju.edu.cn/overcovid/). The publicly available webservers, databases and tools associated with SARS-CoV-2 have been incorporated in the resource page. In addition, a network view of the resources is provided to display the scope of the research. Other information like SARS-CoV-2 strain...

Genome-wide association studies (GWAS) play a vital role in identifying important genes those is associated with the phenotypic variations of living organisms. There are several statistical methods for GWAS including the linear mixed model (LMM) which is popular for addressing the challenges of hidden population stratification and polygenic effects. However, most of these methods including LMM are sensitive to phenotypic outliers that may lead the misleading results. To overcome this problem, in this paper, we proposed a way to robustify the LMM approach for reducing the influence of outlying observations using the β-divergence method. The performance of the proposed method was investigated using both synthetic and real data analysis. Simulation results showed that the proposed method performs better than both linear regression model (LRM) and LMM approaches in terms of powers and false discovery rates in presence of phenotypic outliers. On the other hand, the proposed method perfor...

Flowering time is an important agronomic trait, attributed by multiple genes, gene–gene interactions and environmental factors. Population stratification and polygenic effects might confound genetic effects of the causal loci underlying this complex trait. We proposed a two-step approach for detecting epistasis interactions underlying rice flowering time by accounting population structure and polygenic effects. Simulation studies showed that the approach used in this study performs better than classical and PC-linear approaches in terms of powers and false discovery rates in the case of population stratification and polygenic effects. Whole genome epistasis analyses identified 589 putative genetic interactions for flowering time. Eighteen of these interactions are located within 10 kilobases of regions of known protein–protein interactions. Thirty-seven SNPs near to twenty-five genes involve in rice or/and Arabidopsis (orthologue) flowering pathway. Bioinformatics analysis showed th...

Morphological traits played an important role in vegetative growth of cotton (Gossypium hirsutum L.), and also had an critical impact on reproductive growth. In this study, we dissected the genetic architecture of four morphological traits, including plant height (PLH), stem diameter (STD), stem first (STF) and stem node (STN). Thirty-nine lines and their 178 F1 hybrids of Upland cotton grown in three environments were used for association mapping. The association mapping was conducted using mixed linear model approaches for analyzing full genetic model with genetic effects of additive, dominance, epistasis and their environmental interaction. The results showed that 25 highly significant quantitative trait SSRs (QTSs) were detected and their total heritability was high for the four morphological traits studied (h2G+GE≈63.08%-78.28%). It was revealed that additive, dominance and their environmental interaction effects were important genetic recourses for morphological traits in cotton. This research provides new insights into cotton quantitative genetics and molecular breeding.

A rapid on-site detection of exogenous proteins without the need for equipped laboratories or skilled personnel would benefit many areas. We built a rapid protein detection platform based on aptamer-induced inner-membrane scaffolds dimerization by virtue of bacterial ghost system. When the detection platform was coincubated with two kinds of aptamers targeting two different sites of thrombin, green fluorescence or β-lactamase activity were yielded with two different designs. The latter was detected by commercially available testing strips.

Genetic architecture of branch traits has large influences on the morphological structure, photosynthetic capacity, planting density, and yield of Upland cotton (Gossypium hirsutum L.). This research aims to reveal the genetic effects of six branch traits, including bottom fruit branch node number (BFBNN), bottom fruit branch length (BFBL), middle fruit branch node number (MFBNN), middle fruit branch length (MFBL), upper fruit branch node number (UFBNN), and upper fruit branch length (UFBL). Association mapping was conducted for these traits of 39 lines and their 178 F 1 hybrids in three environments. There were 20 highly significant Quantitative Trait SSRs (QTSs) detected by mixed linear model approach analyzing a full genetic model with genetic effects of additive, dominance, epistasis and their environment interaction. The phenotypic variation explained by genetic effects ranged from 32.64 ~ 91.61%, suggesting these branch traits largely influenced by genetic factors.

Startle behavior is important for survival, and abnormal startle responses are related to several neurological diseases. Drosophila melanogaster provides a powerful system to investigate the genetic underpinnings of variation in startle behavior. Since mechanically induced, startle responses and environmental conditions can be readily quantified and precisely controlled. The 156 wild-derived fully sequenced lines of the Drosophila Genetic Reference Panel (DGRP) were used to identify SNPs and transcripts associated with variation in startle behavior. The results validated highly significant effects of 33 quantitative trait SNPs (QTSs) and 81 quantitative trait transcripts (QTTs) directly associated with phenotypic variation of startle response. We also detected QTT variation controlled by 20 QTSs (tQTSs) and 73 transcripts (tQTTs). Association mapping based on genomic and transcriptomic data enabled us to construct a complex genetic network that underlies variation in startle behavior. Based on principles of evolutionary conservation, human orthologous genes could be superimposed on this network. This study provided both genetic and biological insights into the variation of startle response behavior of Drosophila melanogaster, and highlighted the importance of genetic network to understand the genetic architecture of complex traits.

We conducted a meta-analysis of genome-wide association studies (GWAS) with ~16 million genotyped/imputed genetic variants in 62,892 type 2 diabetes (T2D) cases and 596,424 controls of European ancestry. We identified 139 common and 4 rare (minor allele frequency < 0.01) variants associated with T2D, 42 of which (39 common and 3 rare variants) were independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2,765) and other T2D-relevant tissues (í µí±› = up to 385) with the GWAS results identified 33 putative functional genes for T2D, three of which were targeted by approved drugs. A further integration of DNA methylation (í µí±› = 1,980) and epigenomic annotations data highlighted three putative T2D genes (CAMK1D, TP53INP1 and ATP5G1) with plausible regulatory mechanisms whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. We further found evidence that the T2D-associated loci have been under purifying selection.

We develop a Bayesian mixed linear model that simultaneously estimates single-nucleotide polymorphism (SNP)-based heritability, polygenicity (proportion of SNPs with nonzero effects), and the relationship between SNP effect size and minor allele frequency for complex traits in conventionally unrelated individuals using genome-wide SNP data. We apply the method to 28 complex traits in the UK Biobank data (N = 126,752) and show that on average, 6% of SNPs have nonzero effects, which in total explain 22% of phenotypic variance. We detect significant (P < 0.05/28) signatures of natural selection in the genetic architecture of 23 traits, including reproductive, cardiovascular, and anthropometric traits, as well as educational attainment. The significant estimates of the relationship between effect size and minor allele frequency in complex traits are consistent with a model of negative (or purifying) selection, as confirmed by forward simulation. We conclude that negative selection acts pervasively on the genetic variants associated with human complex traits.

Type 2 diabetes (T2D) is a very common disease in humans. Here we conduct a meta-analysis of genome-wide association studies (GWAS) with ~16 million genetic variants in 62,892 T2D cases and 596,424 controls of European ancestry. We identify 139 common and 4 rare variants associated with T2D, 42 of which (39 common and 3 rare variants) are independent of the known variants. Integration of the gene expression data from blood (n = 14,115 and 2765) with the GWAS results identifies 33 putative functional genes for T2D, 3 of which were targeted by approved drugs. A further integration of DNA methylation (n = 1980) and epigenomic annotation data highlight 3 genes (CAMK1D, TP53INP1, and ATP5G1) with plausible regulatory mechanisms, whereby a genetic variant exerts an effect on T2D through epigenetic regulation of gene expression. Our study uncovers additional loci, proposes putative genetic regulatory mechanisms for T2D, and provides evidence of purifying selection for T2D-associated variants.

Genotype-by-environment interaction (GEI) is a fundamental component in understanding 24 complex trait variation. However, it remains challenging to identify genetic variants with GEI 25 effects in humans largely because of the small effect sizes and the difficulty of monitoring 26 environmental fluctuations. Here, we demonstrate that GEI can be inferred from genetic 27 variants associated with phenotypic variability in a large sample without the need of measuring 28 environmental factors. We performed a genome-wide variance quantitative trait locus (vQTL) 29 analysis of ~5.6 million variants on 348,501 unrelated individuals of European ancestry for 13 30 quantitative traits in the UK Biobank, and identified 75 significant vQTLs with P<2.0´10 -9 for 9 31 traits, especially for those related to obesity. Direct GEI analysis with five environmental factors 32 showed that the vQTLs were strongly enriched with GEI effects. Our results indicate pervasive 33 GEI effects for obesity-related traits and demonstrate the detection of GEI without 34 environmental data.

Observational epidemiological studies have found an association between schizophrenia and breast cancer, but it is not known if the relationship is a causal one. We used summary statistics from very large genome-wide association studies of schizophrenia (n = 40 675 cases and 64 643 controls) and breast cancer (n = 122 977 cases and 105 974 controls) to investigate whether there is evidence that the association is partly due to shared genetic risk factors and whether there is evidence of a causal relationship. Using LD-score regression, we found that there is a small but significant genetic correlation (rG) between the 2 disorders (rG = 0.14, SE = 0.03, P = 4.75 × 10 -8 ), indicating shared genetic risk factors. Using 142 genetic variants associated with schizophrenia as instrumental variables that are a proxy for having schizophrenia, we estimated a causal effect of schizophrenia on breast cancer on the observed scale as b xy = 0.032 (SE = 0.009, P = 2.3 × 10 -4 ). A 1 SD increase in liability to schizophrenia increases risk of breast cancer 1.09-fold. In contrast, the estimated causal effect of breast cancer on schizophrenia from 191 instruments was not significantly different from zero (b xy = −0.005, SE = 0.012, P = .67). No evidence for pleiotropy was found and adjusting for the effects of smoking or parity did not alter the results. These results provide evidence that the previously observed association is due to schizophrenia causally increasing risk for breast cancer. Genetic variants may provide an avenue to elucidating the mechanism underpinning this relationship.

Parkinson's disease (PD), with its characteristic loss of nigrostriatal dopaminergic neurons and deposition of α-synuclein in neurons, is often considered a neuronal disorder. However, in recent years substantial evidence has emerged to implicate glial cell types, such as astrocytes and microglia. In this study, we used stratified LD score regression and expression-weighted cell-type enrichment together with several brain-related and cell-type-specific genomic annotations to connect human genomic PD findings to specific brain cell types. We found that PD heritability does not enrich in global and regional brain annotations or brain-related cell-type-specific annotations. Likewise, we found no enrichment of PD susceptibility genes in brain-related cell types. In contrast, we demonstrated a significant enrichment of PD heritability in a curated lysosomal gene set specifically expressed in astrocytic and microglial subtypes. Our results suggest that PD risk loci do not lie in specific cell types or individual brain regions, but rather in global cellular processes to which cell types may have varying vulnerability.