PIP4K2C inhibition reverses autophagic flux impairment induced by SARS-CoV-2.

In search for broad-spectrum antivirals, we discovered a small molecule inhibitor, RMC-113, that potently suppresses the replication of multiple RNA viruses including SARS-CoV-2 in human lung organoids. We demonstrated selective dual inhibition of the lipid kinases PIP4K2C and PIKfyve by RMC-113 and target engagement by its clickable analog. Advanced lipidomics revealed alteration of SARS-CoV-2-induced phosphoinositide signature by RMC-113 and linked its antiviral effect with functional PIP4K2C and PIKfyve inhibition.

Harnessing the predicted maize pan-interactome for putative gene function prediction and prioritization of candidate genes for important traits.

The recent assembly and annotation of the 26 maize nested association mapping population founder inbreds have enabled large-scale pan-genomic comparative studies. These studies have expanded our understanding of agronomically important traits by integrating pan-transcriptomic data with trait-specific gene candidates from previous association mapping results. In contrast to the availability of pan-transcriptomic data, obtaining reliable protein-protein interaction (PPI) data has remained a challenge due to its high cost and complexity.

Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells.

Co-expression pan-network reveals genes involved in complex traits within maize pan-genome.

Background: With the advances in the high throughput next generation sequencing technologies, genome-wide association studies (GWAS) have identified a large set of variants associated with complex phenotypic traits at a very fine scale. Despite the progress in GWAS, identification of genotype-phenotype relationship remains challenging in maize due to its nature with dozens of variants controlling the same trait. As the causal variations results in the change in expression, gene expression analyses carry a pivotal role in unraveling the transcriptional regulatory mechanisms behind the phenotypes.

G4Boost: a machine learning-based tool for quadruplex identification and stability prediction.

Background: G-quadruplexes (G4s), formed within guanine-rich nucleic acids, are secondary structures involved in important biological processes. Although every G4 motif has the potential to form a stable G4 structure, not every G4 motif would, and accurate energy-based methods are needed to assess their structural stability. Here, we present a decision tree-based prediction tool, G4Boost, to identify G4 motifs and predict their secondary structure folding probability and thermodynamic stability based on their sequences, nucleotide compositions, and estimated structural topologies.

Multiple Variant Calling Pipelines in Wheat Whole Exome Sequencing.

The highly challenging hexaploid wheat () genome is becoming ever more accessible due to the continued development of multiple reference genomes, a factor which aids in the plight to better understand variation in important traits. Although the process of variant calling is relatively straightforward, selection of the best combination of the computational tools for read alignment and variant calling stages of the analysis and efficient filtering of the false variant calls are not always easy tasks. Previous studies have analyzed the impact of methods on the quality metrics in diploid organisms.

mirMachine: A One-Stop Shop for Plant miRNA Annotation.

Of different types of noncoding RNAs, microRNAs (miRNAs) have arguably been in the spotlight over the last decade. As post-transcriptional regulators of gene expression, miRNAs play key roles in various cellular pathways, including both development and response to a/biotic stress, such as drought and diseases. Having high-quality reference genome sequences enabled identification and annotation of miRNAs in several plant species, where miRNA sequences are highly conserved.

Genome-wide discovery of G-quadruplexes in barley.

G-quadruplexes (G4s) are four-stranded nucleic acid structures with closely spaced guanine bases forming square planar G-quartets. Aberrant formation of G4 structures has been associated with genomic instability. However, most plant species are lacking comprehensive studies of G4 motifs.

LncMachine: a machine learning algorithm for long noncoding RNA annotation in plants.

Following the elucidation of the critical roles they play in numerous important biological processes, long noncoding RNAs (lncRNAs) have gained vast attention in recent years. Manual annotation of lncRNAs is restricted by known gene annotations and is prone to false prediction due to the incompleteness of available data. However, with the advent of high-throughput sequencing technologies, a magnitude of high-quality data has become available for annotation, especially for plant species such as wheat.

Genome-Wide Discovery of G-Quadruplexes in Wheat: Distribution and Putative Functional Roles.

G-quadruplexes are nucleic acid secondary structures formed by a stack of square planar G-quartets. G-quadruplexes were implicated in many biological functions including telomere maintenance, replication, transcription, and translation, in many species including humans and plants. For wheat, however, though it is one of the world's most important staple food, no G-quadruplex studies have been reported to date.

Long Non-coding RNA in Plants in the Era of Reference Sequences.

The discovery of non-coding RNAs (ncRNAs), and the subsequent elucidation of their functional roles, was largely delayed due to the misidentification of non-protein-coding parts of DNA as "junk DNA," which forced ncRNAs into the shadows of their protein-coding counterparts. However, over the past decade, insight into the important regulatory roles of ncRNAs has led to rapid progress in their identification and characterization. Of the different types of ncRNAs, long non-coding RNAs (lncRNAs), has attracted considerable attention due to their mRNA-like structures and gene regulatory functions in plant stress responses.

Assembly and Annotation of Transcriptome Provided Evidence of miRNA Mobility between Wheat and Wheat Stem Sawfly.

Wheat Stem Sawfly (WSS), Norton (Hymenoptera: Cephidae), is one of the most important pests, causing yield and economic losses in wheat and barley. The lack of information about molecular mechanisms of WSS for defeating plant's resistance prevents application of effective pest control strategies therefore, it is essential to identify the genes and their regulators behind WSS infestations. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are recognized with their regulatory functions on gene expression, tuning protein production by controlling transcriptional and post-transcriptional activities.

RNA Sequencing and Co-expressed Long Non-coding RNA in Modern and Wild Wheats.

There is an urgent need for the improvement of drought-tolerant bread and durum wheat. The huge and complex genome of bread wheat (BBAADD genome) stands as a vital obstruction for understanding the molecular mechanism underlying drought tolerance. However, tetraploid wheat (Triticum turgidum ssp.

Leveling the Playing Field in Homozygosity Mapping Using Map Distances.

Studies of linkage disequilibrium (LD) and its variation in the genome are of central importance for understanding evolutionary history, population structure, and selective sweeps. Extreme forms of the latter may result in runs of homozygosity (ROH). In human gene mapping, long ROHs are the basis for homozygosity mapping (HM) with length measured in terms of Mb (10 base pairs physical distance).