Biology subjects

Chu, C.

Publications and source records attributed to Chu, C..

80 records · Page 5Linked to original sources

bioRxiv2019

Hierarchy of connectivity-function relationship of the human cortex revealed through predicting activity across functional domains

Many studies showed that anatomical connectivity supports both anatomical and functional hierarchies that span across the primary and association cortices in the cerebral cortex. However, it remains unclear whether a hierarchy of connectivity-function relationship (CFR) exists across the human cortex as well as how to characterize the hierarchy of this CFR if it exists. We first addressed whether anatomical connectivity could be used to predict functional activations across different functional domains using multilinear regression models. Then we characterized the CFR by predicting activity from anatomical connectivity throughout the cortex. We found that there is a hierarchy of CFR across the human cortex. Moreover, this CFR hierarchy was correlated to the functional and anatomical hierarchy reflected in functional flexibility, functional variability, and the myelin map. Our results suggest a shared hierarchical mechanism in the cortex, a finding which provides important insights into the anatomical and functional organization of the human brain.

neuroscience↗

bioRxiv2018

Characterization of functional diversity of the human brain based on intrinsic connectivity networks

Spontaneous fluctuations underlying the brain activity can reflect the intrinsic organization of the system, such as the functional brain networks. In large scale, a network perspective has emerged as a new avenue to explore the functional properties of human brain. Here, we studied functional diversity in healthy subjects based on the network perspective. We hypothesized that the patterns of participation of different functional networks were related with the functional diversity of particular brain regions. Independent component analysis (ICA) was adopted to detect the intrinsic connectivity networks (ICNs) based on the data of resting-state functional MRI. An index of functional diversity (FD index) was proposed to quantitatively describe the degree of anisotropic distribution related with participation of various ICNs. We found that FD index continuously varied across the brain, for example, the primary motor cortex with low FD value and the precuneus with significantly high FD value. The FD values indicated the different functional roles of the corresponding brain regions, which were reflected by the various patterns of participation of ICNs. The FD index can be used as a new approach to quantitatively characterize the functional diversity of human brain, even for the changed functional properties caused by the psychiatric disorders.

neuroscience↗

bioRxiv2018

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3,337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc) -three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. CpG sites associated with hippocampus volume were significantly enriched within cancer-related genes and within regulatory elements containing the transcriptionally repressive histone H3K27 tri-methylation mark that is vital for stem cell fate specification. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

genomics↗

bioRxiv2018

Genome-wide association and functional studies identify 46 novel loci for alcohol consumption and suggest common genetic mechanisms with neuropsychiatric disorders

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. We conducted a genome-wide association study (GWAS) of alcohol use in ~480,000 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 novel, common loci, and investigated their potential functional significance using magnetic resonance imaging data, gene expression and behavioral studies in Drosophila. Our results identify new genetic pathways associated with alcohol consumption and suggest common genetic mechanisms with several neuropsychiatric disorders including schizophrenia.

genetics↗

bioRxiv2018

CLADES: A Classification-based Machine Learning Method for Species Delimitation from Population Genetic Data

Species are considered to be the basic unit of ecological and evolutionary studies. Since multi-locus genomic data are becoming increasingly available, there has been considerable interests in the use of DNA sequence data to delimit species. In this paper, we show that machine learning can be used for species delimitation. There exists no species delimitation methods that are based on machine learning. Our method treats the species delimitation problem as a classification problem. It is a problem of identifying the category of a new observation on the basis of training data. Extensive simulation is first conducted over a broad range of evolutionary parameters for training purpose. Each pair of known populations are combined to form training samples with a label of \"same species\" or \"different species\". We use Support Vector Machine (SVM) to train a classifier using a set of summary statistics computed from training samples as features. The trained classifier can classify a test sample to two outcomes: \"same species\" or \"different species\". Given multi-locus genomic data of multiple related organisms or populations, our method (called CLADES) performs species delimitation by first classifying pairs of populations. CLADES then delimits species by maximizing the likelihood of species assignment for multiple populations. CLADES is evaluated through extensive simulation and also tested on real genetic data. We show that CLADES is both accurate and efficient for species delimitation when compared with existing methods. CLADES can be useful especially when existing methods have difficulty in delimitation, e.g. with short species divergence time and gene flow.

evolutionary biology↗

bioRxiv2017

OMSV enables accurate and comprehensive identification of large structural variations from nanochannel-based single-molecule optical maps

Human genomes contain structural variations (SVs) that are associated with various phenotypic variations and diseases. SV detection by sequencing is incomplete due to limited read length. Nanochannel-based optical mapping (OM) allows direct observation of SVs up to hundreds of kilo-bases in size on individual DNA molecules, making it a promising alternative technology for identifying large SVs. SV detection from optical maps is non-trivial due to complex types of error present in OM data, and no existing methods can simultaneously handle all these complex errors and the wide spectrum of SV types. Here we present a novel method, OMSV, for accurate and comprehensive identification of SVs from optical maps. OMSV detects both homozygous and heterozygous SVs, SVs of various types and sizes, and SVs with and without creating/destroying restriction sites. In an extensive series of tests based on real and simulated data, OMSV achieved both high sensitivity and specificity, with clear performance gains over the latest existing method. Applying OMSV to a human cell line, we identified hundreds of SVs >2kbp, with 65% of them missed by sequencing-based callers. Independent experimental validations confirmed the high accuracy of these SVs. We also demonstrate how OMSV can incorporate sequencing data to determine precise SV break points and novel sequences in the SVs not contained in the reference. We provide OMSV as open-source software to facilitate systematic studies of large SVs.

bioinformatics↗

bioRxiv2017

CircMarker: A Fast and Accurate Algorithm for Circular RNA Detection

While RNA is often created from linear splicing during transcription, recent studies have found that non-canonical splicing sometimes occurs. Non-canonical splicing joins 3 and 5 and forms the socalled circular RNA. It is now believed that circular RNA plays important biological roles such as affecting susceptibility in some diseases. within these few years, several experimental methods have been developed to enrich circular RNA while degrade linear RNA. Although several useful software tools for circRNA detection have been developed as well, these tools may miss many circular RNA. Also, existing tools are slow for large data because those tools often depend on reads mapping. In this paper, we present a new computational approach, named CircMarker, based on k-mers rather than reads mapping for circular RNA detection. CircMarker takes advantage of transcriptome annotation files to create k-mer table for circular RNA detection. Empirical results show that CircMarker outperforms existing tools in circular RNA detection on accuracy and efficiency in many simulated and real datasets. CircMarker can be downloaded from https://github.com/lxwgcool/CircMarker.

bioinformatics↗

bioRxiv2017

GAPPadder: A Sensitive Approach for Closing Gaps on Draft Genomes with Short Sequence Reads

BackgroundClosing gaps in draft genomes is an important post processing step in genome assembly. It leads to more complete genomes, which benefits downstream genome analysis such as annotation and genotyping. Several tools have been developed for gap closing. However, these tools dont fully utilize the information contained in the sequence data. For example, while it is known that many gaps are caused by genomic repeats, existing tools often ignore many sequence reads that originate from a repeat-related gap.\n\nResultsIn this paper, we propose a new approach called GAPPadder for gap closing. The main advantage of GAPPadder is that it uses more information in sequence data for gap closing. In particular, GAPPadder finds and uses reads that originate from repeate-related gaps. We show that these repeat-associated reads are useful for gap closing, even though they are ignored by all existing tools. Other main features of GAPPadder include utilizing the information in sequence reads with different insert sizes and performing two-stage local assembly of gap sequences. We compare GAPPadder with GapCloser, GapFiller and Sealer on one bacterial genome, human chromosome 14 and the human whole genome with paired-end and mate-paired reads with both short and long insert sizes. Empirical results show that GAPPadder can close more gaps than these existing tools. Besides closing gaps on draft genomes assembled only from short sequence reads, GAPPadder can also be used to close gaps for draft genomes assembled with long reads. We show GAPPadder can close gaps on the bed bug genome and the Asian sea bass genome that are assembled partially and fully with long reads respectively. We also show GAPPadder is efficient in both time and memory usage. The software tool, GAPPadder, is available for download at https://github.com/Reedwarbler/GAPPadder.

bioinformatics↗