Biology subjects

Wei, X.

Publications and source records attributed to Wei, X..

258 records · Page 15Linked to original sources

bioRxiv2017

Mid-Infrared Spectroscopy Study of Effects of Neonicotinoids on Forager Honey Bee (Apis mellifera) Fat Bodies and Their Connection to Colony Collapse Disorder

This study investigated the negative effects of neonicotinoid pesticides on honey bees in environment surrounding areas of pesticide use. The aim of the experiment is to identify possible contributors to the sudden decrease in honey bee population over the past 60 years, a phenomenon known as Colony Collapse Disorder. Analysis was performed on three sets of bees: the control group which was not in contact with pesticides, the infected dead group which was a set of bees suspected to have died due to neonicotinoids, and the infected alive group which was suspected to be under the influence of neonicotinoids. After dissecting the bee samples and extracting their fat bodies, the chemical composition and protein structures of the samples were analyzed using Mid-Infrared Beamline at the Canadian Light Source. Results from the spectra of bee samples exposed to neonicotinoids demonstrated possible residual pesticide chemicals within fat bodies. Several spectral peaks were also correlated with a possible change in protein secondary structures from primarily {beta}-sheet to -helix within fat bodies of neonicotinoid-affected bees. It is likely that the pesticides caused the growth of additional -helical structures, which is consistent with consequences of the inhibition of nicotinic acetylcholine receptors (nAChRs) a current pathway of harm of Colony Collapse Disorder as identified in past literature.

pharmacology and toxicology↗

bioRxiv2017

A Large-Scale Binding and Functional Map of Human RNA Binding Proteins

Genomes encompass all the information necessary to specify the development and function of an organism. In addition to genes, genomes also contain a myriad of functional elements that control various steps in gene expression. A major class of these elements function only when transcribed into RNA as they serve as the binding sites for RNA binding proteins (RBPs), which act to control post-transcriptional processes including splicing, cleavage and polyadenylation, RNA editing, RNA localization, stability, and translation. Despite the importance of these functional RNA elements encoded in the genome, they have been much less studied than genes and DNA elements. Here, we describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. These data expand the catalog of functional elements encoded in the human genome by addition of a large set of elements that function at the RNA level through interaction with RBPs.\n\nHighlightsO_LI223 eCLIP datasets for 150 RBPs reveal a wide variety of in vivo RNA target classes.\nC_LIO_LI472 knockdown/RNA-seq profiles of 263 RBPs reveal factor-responsive targets and integration with eCLIP indicates RNA expression and splicing regulatory patterns.\nC_LIO_LI78 RNA Bind-N-Seq profiles of in vitro binding motifs reveal links between in vitro and in vivo binding and indicate that eCLIP peaks that contain in vitro motifs are more strongly associated with regulation.\nC_LIO_LI274 maps of RBP subcellular localization by immunofluorescence indicate widespread organelle-specific RNA processing regulation.\nC_LIO_LI63 ChIP-seq profiles of DNA association suggest broad interconnectivity between chromatin association and RNA processing.\nC_LI

genomics↗

bioRxiv2017

A group of nuclear factor Y transcription factors are likely sub-functionalized in the endosperm development of rice and other monocots

Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor that consists of three subunits, NF-YA, NF-YB, and NF-YC. Although NF-Ys play multiple roles in plant development, their functions during endosperm development are not well understood. In this study, we identified eight NF-Y encoding genes, including OsNF-YA8, OsNF-YB1,9, and OsNF-YC8,9,10,11,12, which predominantly express in the rice endosperm. Interestingly, the closest homologs of these OsNF-Ys are present only in the monocot species. All the genes are preferentially expressed in the endosperm, suggesting their roles in the regulation of endosperm development. A systemic analysis of the interactions between rice endosperm-preferential NF-Ys in yeast revealed that NF-YBs and NF-YCs could interact with each other. OsNF-YA8 is a recently evolved NF-YA in rice. Generally, NF-YA does not interact with NF-YB monomers in plants; however, in the present study, we found that OsNY-YA8 interacts with OsNF-YB9. Our results also indicated that the endosperm-preferential OsNF-YBs and OsNF-YCs could interact with some ethylene response factors (ERFs) of rice. Unlike the OsNF-YC8,9,10, the members of OsNF-YB1, 9 or OsNF-YC 11 and 12 showed lack of transcriptional activation when present alone. However, they displayed functional activity while in dimer form. In addition, OsNF-YB1 knockout lines showed significant changes in the seed morphology, further confirms its role in endosperm development. Our findings have provided strong evidences that the group of phylogenetically conserved NF-Ys are differentiated in monocots to regulate the endosperm development.

plant biology↗

bioRxiv2017

Novel Pedigree Analysis Implicates DNA Repair And Chromatin Remodeling In Multiple Myeloma Risk

The high-risk pedigree (HRP) design is an established strategy to discover rare, highly-penetrant, Mendelian-like causal variants. Its success, however, in complex traits has been modest, largely due to challenges of genetic heterogeneity and complex inheritance models. We describe a HRP strategy that addresses intra-familial heterogeneity, and identifies inherited segments important for mapping regulatory risk. We apply this new Shared Genomic Segment (SGS) method in 11 extended, Utah, multiple myeloma (MM) HRPs, and subsequent exome sequencing in SGS regions of interest in 1063 MM / MGUS (monoclonal gammopathy of undetermined significance - a precursor to MM) cases and 964 controls from a jointly-called collaborative resource, including cases from the initial 11 HRPs. One genome-wide significant 1.8 Mb shared segment was found at 6q16. Exome sequencing in this region revealed predicted deleterious variants in USP45 (p.Gln691*, p.Gln621Glu), a gene known to influence DNA repair through endonuclease regulation. Additionally, a 1.2 Mb segment at 1p36.11 is inherited in two Utah HRPs, with coding variants identified in ARID1A (p.Ser90Gly, p.Met890Val), a key gene in the SWI/SNF chromatin remodeling complex. Our results provide compelling statistical and genetic evidence for segregating risk variants for MM. In addition, we demonstrate a novel strategy to use large HRPs for risk-variant discovery more generally in complex traits.\n\nAUTHOR SUMMARYAlthough family-based studies demonstrate inherited variants play a role in many common and complex diseases, finding the genes responsible remains a challenge. High-risk pedigrees, or families with more disease than expected by chance, have been helpful in the discovery of variants responsible for less complex diseases, but have not reached their potential in complex diseases. Here, we describe a method to utilize high-risk pedigrees to discover risk-genes in complex diseases. Our method is appropriate for complex diseases because it allows for genetic-heterogeneity, or multiple causes of disease, within a pedigree. This method allows us to identify shared segments that likely harbor disease-causing variants in a family. We apply our method in Multiple Myeloma, a heritable and complex cancer of plasma cells. We identified two genes USP45 and ARID1A that fall within shared segments with compelling statistical evidence. Exome sequencing of these genes revealed likely-damaging variants inherited in Myeloma high-risk families, suggesting these genes likely play a role in development of Myeloma. Our Myeloma findings demonstrate our high-risk pedigree method can identify genetic regions of interest in large high-risk pedigrees that are also relevant to smaller nuclear families and overall disease risk. In sum, we offer a strategy, applicable across phenotypes, to revitalize high-risk pedigrees in the discovery of the genetic basis of common and complex disease.

genetics↗

bioRxiv2017

Interactome INSIDER: A Multi-Scale Structural Interactome Browser For Genomic Studies

Protein interactions underlie nearly all known cellular function, making knowledge of their binding conformations paramount to understanding the physical workings of the cell. Studying binding conformations has allowed scientists to explore some of the mechanistic underpinnings of disease caused by disruption of protein interactions. However, since experimentally determined interaction structures are only available for a small fraction of the known interactome such inquiry has largely excluded functional genomic studies of the human interactome and broad observations of the inner workings of disease. Here we present Interactome INSIDER, an information center for genomic studies using the first full-interactome map of human interaction interfaces. We applied a new, unified framework to predict protein interaction interfaces for 184,605 protein interactions with previously unresolved interfaces in human and 7 model organisms, including the entire experimentally determined human binary interactome. We find that predicted interfaces share several known functional properties of interfaces, including an enrichment for disease mutations and recurrent cancer mutations, suggesting their applicability to functional genomic studies. We also performed 2,164 de novo mutagenesis experiments and show that mutations of predicted interface residues disrupt interactions at a similar rate to known interface residues and at a much higher rate than mutations outside of predicted interfaces. To spur functional genomic studies in the human interactome, Interactome INSIDER (http://interactomeinsider.yulab.org) allows users to explore known population variants, disease mutations, and somatic cancer mutations, or upload their own set of mutations to find enrichment at the level of protein domains, residues, and 3D atomic clustering in known and predicted interaction interfaces.

genomics↗

bioRxiv2016

The complex sequence landscape of maize revealed by single molecule technologies

Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate elucidation of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here, we report the assembly and annotation of maize, a genetic and agricultural model species, using Single Molecule Real-Time (SMRT) sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and significant improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed over 130,000 intact transposable elements (TEs), allowing us to identify TE lineage expansions unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by SMRT sequencing. In addition, comparative optical mapping of two other inbreds revealed a prevalence of deletions in the low gene density region and maize lineage-specific genes.

genomics↗