SPECS: a non-parametric method to identify tissue-specific molecular features for unbalanced sample groups

Background To understand biology and differences among various tissues or cell types, one typically searches for molecular features that display characteristic abundance patterns. Several specificity metrics have been introduced to identify tissue-specific molecular features, but these either require an equal number of replicates per tissue or they can’t handle replicates at all. Results We describe a non-parametric specificity score that is compatible with unequal sample group sizes. To demonstrate its usefulness, the specificity score was calculated on all GTEx samples, detecting known and novel tissue-specific genes. A webtool was developed to browse these results for genes or tissues of interest. An example python implementation of SPECS is available at https://github.com/celineeveraert/SPECS. The precalculated SPECS results on the GTEx data are available through a user-friendly browser at specs.cmgg.be. Conclusions SPECS is a non-parametric method that identifies known and novel specific-expressed genes. In addition, SPECS could be adopted for other features and applications

Dynamic Patterns of Transcript Abundance of Transposable Element Families in Maize.

Transposable Elements (TEs) are mobile elements that contribute the majority of DNA sequences in the maize genome. Due to their repetitive nature, genomic studies of TEs are complicated by the difficulty of properly attributing multi-mapped short reads to specific genomic loci. Here, we utilize a method to attribute RNA-seq reads to TE families rather than particular loci in order to characterize transcript abundance for TE families in the maize genome. We applied this method to assess per-family expression of transposable elements in >800 published RNA-seq libraries representing a range of maize development, genotypes, and hybrids. While a relatively small proportion of TE families are transcribed, expression is highly dynamic with most families exhibiting tissue-specific expression. A large number of TE families were specifically detected in pollen and endosperm, consistent with reproductive dynamics that maintain silencing of TEs in the germ line. We find that B73 transcript abundance is a poor predictor of TE expression in other genotypes and that transcript levels can differ even for shared TEs. Finally, by assessing recombinant inbred line and hybrid transcriptomes, complex patterns of TE transcript abundance across genotypes emerged. Taken together, this study reveals a dynamic contribution of TEs to maize transcriptomes

Comparison Between Expression Microarrays and RNA-Sequencing Using UKBEC Dataset Identified a trans-eQTL Associated with MPZ Gene in Substantia Nigra

In recent years, the advantages of RNA-sequencing (RNA-Seq) have made it the platform of choice for measuring gene expression over traditional microarrays. However, RNA-Seq comes with bioinformatical challenges and higher computational costs. Therefore, this study set out to assess whether the increased depth of transcriptomic information facilitated by RNA-Seq is worth the increased computation over microarrays, specifically at three levels: absolute expression levels, differentially expressed genes identification, and expression QTL (eQTL) mapping in regions of the human brain. Using the United Kingdom Brain Expression Consortium (UKBEC) dataset, there is high agreement of gene expression levels measured by microarrays and RNA-seq when quantifying absolute expression levels and when identifying differentially expressed genes. These findings suggest that depending on the aims of a study, the relative ease of working with microarray data may outweigh the computational time and costs of RNA-Seq pipelines. On the other, there was low agreement when mapping eQTLs. However, a number of eQTLs associated with genes that play important roles in the brain were found in both platforms. For example, a trans-eQTL was mapped that is associated with the MPZ gene in the substantia nigra. These eQTLs that we have highlighted are extremely promising candidates that merit further investigation

Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics

Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter the target's expression or function, as a tool to anticipate the effect of drug action on the same target. Here we apply MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets are further prioritized using independent replication, co-localization, protein expression profiles and data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with blood lipids (HDL-C, LDL-C and triglycerides), we robustly prioritize 30 targets that might elicit beneficial effects in the prevention or treatment of CHD, including NPC1L1 and PCSK9, the targets of drugs used in CHD prevention. We discuss how this approach can be generalized to other targets, disease biomarkers and endpoints to help prioritize and validate targets during the drug development process

Transcriptional signatures of wheat inforescence development

In order to maintain global food security, it will be necessary to increase yields of the cereal crops that provide most of the calories and protein for the world’s population, which includes common wheat (Triticum aestivum L.). An important wheat yield component is the number of grain-holding spikelets which form on the spike during inflorescence development. Characterizing the gene regulatory networks controlling the timing and rate of inflorescence development will facilitate the selection of natural and induced gene variants that contribute to increased spikelet number and yield. In the current study, co-expression and gene regulatory networks were assembled from a temporal wheat spike transcriptome dataset, revealing the dynamic expression profiles associated with the progression from vegetative meristem to terminal spikelet formation. Consensus co-expression networks revealed enrichment of several transcription factor families at specific developmental stages including the sequential activation of different classes of MIKC-MADS box genes. This gene regulatory network highlighted interactions among a small number of regulatory hub genes active during terminal spikelet formation. Finally, the CLAVATA and WUSCHEL gene families were investigated, revealing potential roles for TtCLE13, TtWOX2, and TtWOX7 in wheat meristem development. The hypotheses generated from these datasets and networks further our understanding of wheat inflorescence development. IntroductionFil: VanGessel, Carl. Colorado State University; Department of Soil and Crop Sciences; Estados UnidosFil: Hamilton, James. Colorado State University; Department of Soil and Crop Sciences; Estados UnidosFil: Tabbita, Facundo. Universidad de Córdoba. Escuela Técnica Superior de Ingeniería Agronómica y de Montes. Departamento de Genética; España. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Dubcovsky, Jorge. University of California, Department of Plant Sciences; Estados Unidos. Howard Hughes Medical Institute; Estados UnidosFil: Pearce, Stephen. Rothamsted Research. Sustainable Soils and Crops; Reino Unido. Colorado State University; Department of Soil and Crop Sciences; Estados Unido

Sex-specific selection drives the evolution of alternative splicing in birds

Males and females of the same species share the majority of their genomes, yet they are frequently exposed to conflicting selection pressures. Gene regulation is widely assumed to resolve these conflicting sex-specific selection pressures, and although there has been considerable focus on elucidating the role of gene expression level in sex-specific adaptation, other regulatory mechanisms have been overlooked. Alternative splicing enables different transcripts to be generated from the same gene, meaning that exons which have sex-specific beneficial effects can in theory be retained in the gene product, while exons with detrimental effects can be skipped. However, at present, little is known about how sex-specific selection acts on broad patterns of alternative splicing. Here we investigate alternative splicing across males and females of multiple bird species. We identify hundreds of genes that have sex-specific patterns of splicing, and establish that sex differences in splicing are correlated with phenotypic sex differences. Additionally, we find that alternatively spliced genes have evolved rapidly as a result of sex-specific selection, and suggest that sex differences in splicing offer another route to sex-specific adaptation when gene expression level changes are limited by functional constraints. Overall, our results shed light on how a diverse transcriptional framework can give rise to the evolution of phenotypic sexual dimorphism

Transcriptional signatures of wheat inflorescence development

In order to maintain global food security, it will be necessary to increase yields of the cereal crops that provide most of the calories and protein for the world’s population, which includes common wheat (Triticum aestivum L.). An important wheat yield component is the number of grain-holding spikelets which form on the spike during inflorescence development. Characterizing the gene regulatory networks controlling the timing and rate of inflorescence development will facilitate the selection of natural and induced gene variants that contribute to increased spikelet number and yield. In the current study, co-expression and gene regulatory networks were assembled from a temporal wheat spike transcriptome dataset, revealing the dynamic expression profiles associated with the progression from vegetative meristem to terminal spikelet formation. Consensus co-expression networks revealed enrichment of several transcription factor families at specific developmental stages including the sequential activation of different classes of MIKC-MADS box genes. This gene regulatory network highlighted interactions among a small number of regulatory hub genes active during terminal spikelet formation. Finally, the CLAVATA and WUSCHEL gene families were investigated, revealing potential roles for TtCLE13, TtWOX2, and TtWOX7 in wheat meristem development. The hypotheses generated from these datasets and networks further our understanding of wheat inflorescence developme

The chromosome-scale genome assembly of the yellowtail clownfish Amphiprion clarkii provides insights into the melanic pigmentation of anemonefish

Anemonefish are an emerging group of model organisms for studying genetic, ecological, evolutionary, and developmental traits of coral reef fish. The yellowtail clownfish Amphiprion clarkii possesses species-specific characteristics such as inter-species co-habitation, high intra-species color variation, no anemone specificity, and a broad geographic distribution, that can increase our understanding of anemonefish evolutionary history, behavioral strategies, fish-anemone symbiosis, and color pattern evolution. Despite its position as an emerging model species, the genome of A. clarkii is yet to be published. Using PacBio long-read sequencing and Hi-C chromatin capture technology, we generated a high-quality chromosome-scale genome assembly initially comprised of 1, 840 contigs with an N50 of 1, 203, 211 bp. These contigs were successfully anchored into 24 chromosomes of 843, 582, 782 bp and annotated with 25, 050 protein-coding genes encompassing 97.0% of conserved actinopterygian genes, making the quality and completeness of this genome the highest among all published anemonefish genomes to date. Transcriptomic analysis identified tissue-specific gene expression patterns, with the brain and optic lobe having the largest number of expressed genes. Further analyses revealed higher copy numbers of erbb3b (a gene involved in melanocyte development) in A. clarkii compared with other anemonefish, thus suggesting a possible link between erbb3b and the natural melanism polymorphism observed in A. clarkii. The publication of this high-quality genome, along with A. clarkii's many unique traits, position this species as an ideal model organism for addressing scientific questions across a range of disciplines