Biology subjects

Wu, C.

Publications and source records attributed to Wu, C..

354 records · Page 20Linked to original sources

bioRxiv2017

Upper Limit for Angular Compounding Speckle Reduction

Previous studies of angular compounding for speckle reduction in optical coherence tomography may not have fully accounted for optical aberrations, which produce unintended spatial averaging and concomitant loss of spatial resolution. We accounted for such aberrations by aligning our system and measuring distortions in the images, and found that speckle reduction by angular compounding was limited. Our theoretical analysis using Monte Carlo simulations indicates that \"pure\" angular compounding over 13{degrees} (our full numerical aperture) can improve the signal-to-noise ratio by no more than a factor of 1.5, significantly lower than values reported in literature. Analysis suggests that illuminating only part of the lens to further reduce speckle also involves a trade-off with resolution roughly equivalent to spatial averaging. We conclude that angular compounding provides substantially less benefit than previously expected.

bioengineering↗

bioRxiv2017

T helper cells modulate intestinal stem cell renewal and differentiation

In the small intestine, a cellular niche of diverse accessory cell types supports the rapid generation of mature epithelial cell types through self-renewal, proliferation, and differentiation of intestinal stem cells (ISCs). However, not much is known about interactions between immune cells and ISCs, and it is unclear if and how immune cell dynamics affect eventual ISC fate or the balance between self-renewal and differentiation. Here, we used single-cell RNA-seq (scRNA-Seq) of intestinal epithelial cells (IECs) to identify new mechanisms for ISC-immune cell interactions. Surprisingly, MHC class II (MHCII) is enriched in two distinct subsets of Lgr5+ crypt base columnar ISCs, which are also distinguished by higher proliferation rates. Using co-culture of T cells with intestinal organoids, cytokine stimulations, and in vivo mouse models, we confirm that CD4+ T helper (Th) cells communicate with ISCs and affect their differentiation, in a manner specific to the Th subtypes and their signature cytokines and dependent on MHCII expression by ISCs. Specific inducible knockout of MHCII in intestinal epithelial cells in mice in vivo results in expansion of the ISC pool. Mice lacking T cells have expanded ISC pools, whereas specific depletion of Treg cells in vivo results in substantial reduction of ISC numbers. Our findings show that interactions between Th cells and ISCs mediated via MHCII expressed in intestinal epithelial stem cells help orchestrate tissue-wide responses to external signals.

immunology↗

bioRxiv2017

UniProt Genomic Mapping for Deciphering Functional Effects of Missense Variants

Understanding the association of genetic variation with its functional consequences in proteins is essential for the interpretation of genomic data and identifying causal variants in diseases. Integration of protein function knowledge with genome annotation can assist in rapidly comprehending genetic variation within complex biological processes. Here, we describe mapping UniProtKB human sequences and positional annotations such as active sites, binding sites, and variants to the human genome (GRCh38) and the release of a public genome track hub for genome browsers. To demonstrate the power of combining protein annotations with genome annotations for functional interpretation of variants, we present specific biological examples in disease-related genes and proteins. Computational comparisons of UniProtKB annotations and protein variants with ClinVar clinically annotated SNP data show that 32% of UniProtKB variants co-locate with 8% of ClinVar SNPs. The majority of co-located UniProtKB disease-associated variants (86%) map to pathogenic ClinVar SNPs. UniProt and ClinVar are collaborating to provide a unified clinical variant annotation for genomic, protein and clinical researchers. The genome track hubs, and related UniProtKB files, are downloadable from the UniProt FTP site and discoverable as public track hubs at the UCSC and Ensembl genome browsers.

genomics↗

bioRxiv2017

High throughput expression profiling and in situ screening of circular RNAs in tissues

Circular RNAs (circRNAs) were recently discovered as a class of widely expressed noncoding RNA and have been implicated in regulation of gene expression. However, the function of the majority of circRNAs remains unknown. Studies of circRNAs have been hampered by a lack of essential approaches for detection, quantification and visualization. We therefore developed a target-enrichment sequencing method suitable for high-throughput screening of circRNAs and their linear counterparts. We also applied padlock probes and in situ sequencing to visualize and determine circRNAs localization in human brain tissue at subcellular levels. We measured circRNA abundance across different human samples and tissues. Our results demonstrate the potential of this RNA class to act as a specific diagnostic marker in blood and serum, by detection of circRNAs from genes exclusively expressed in the brain. The powerful and scalable tools we present will enable studies of circRNA function and facilitate screening of circRNA as diagnostic biomarkers.

genomics↗

bioRxiv2017

Embryonic lethality in mice lacking Trim59 due to impaired gastrulation development

TRIM family members have been implicated in a variety of biological processes such as differentiation and development. We here found that Trim59 plays a critical role in early embryo development from blastocyst stage to gastrula. There existed delayed development and empty yolk sacs from embryonic day (E) 8.5 in Trim59 -/- embryos. No viable Trim59 -/- embryos were observed beyond E9.5. Trim59 deficiency affected primary germ layer formation at the beginning of gastrulation. In Trim59 -/- embryos at E6.5 and E7.5, the expression of primary germ layer formation associated genes including Brachyury, lefty2, Cer1, Otx2, Wnt3 and BMP4 was reduced. Homozygous mutant embryonic epiblast was contracted and the mesoderm was absent. Trim59 could interact with actin and myosin associated proteins. Trim59 deficiency disturbed F-actin polymerization during inner cell mass differentiation. Trim59 mediated polymerization of F-actin was via WASH K63-linked ubiquitination. Thus, Trim59 may be a critical regulator for early embryo development from blastocyst stage to gastrula through modulating F-actin assembly.

developmental biology↗

bioRxiv2017

Cross-linking BioThings APIs through JSON-LD to facilitate knowledge exploration

BackgroundApplication Programming Interfaces (APIs) are now widely used to distribute biological data. And many popular biological APIs developed by many different research teams have adopted Javascript Object Notation (JSON) as their primary data format. While usage of a common data format offers significant advantages, that alone is not sufficient for rich integrative queries across APIs.\n\nResultsHere, we have implemented JSON for Linking Data (JSON-LD) technology on the BioThings APIs that we have developed, MyGene.info, MyVariant.info and MyChem.info. JSON-LD provides a standard way to add semantic context to the existing JSON data structure, for the purpose of enhancing the interoperability between APIs. We demonstrated several use cases that were facilitated by semantic annotations using JSON-LD, including simpler and more precise query capabilities as well as API cross-linking.\n\nConclusionsWe believe that this pattern offers a generalizable solution for interoperability of APIs in the life sciences.

bioinformatics↗

bioRxiv2017

Qinichelins, novel catecholate-hydroxamate siderophores synthesized via a multiplexed convergent biosynthesis pathway

The explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites, representing a huge unexploited pool of chemical diversity. Here, we describe the discovery of a novel group of catecholate-hydroxamate siderophores termed qinichelins (2-5) from Streptomyces sp. MBT76. Correlation between the metabolite levels and the protein expression profiles identified the biosynthetic gene cluster (BGC; named qch) most likely responsible for qinichelin biosynthesis. The structure of the molecules was elucidated by bioinformatics, mass spectrometry and NMR. Synthesis of the qinichelins requires the interplay between four gene clusters, for its synthesis and for precursor supply. This biosynthetic complexity provides new insights into the challenges scientists face when applying synthetic biology approaches for natural product discovery.\n\nPride repository reviewer account details:\n\nURL: https://www.ebi.ac.uk/pride/archive/login\n\nProject accession: PXD006577\n\nUsername: reviewer35793@ebi.ac.uk\n\nPassword: 3H0iM1FK

microbiology↗

bioRxiv2017

eGARD: Extracting associations between genomic anomalies and drug responses from text

Tumor molecular profiling plays an integral role in identifying genomic anomalies which may help in personalizing cancer treatments, improving patient outcomes and minimizing risks associated with different therapies. However, critical information regarding the evidence of clinical utility of such anomalies is largely buried in biomedical literature. It is becoming prohibitive for biocurators, clinical researchers and oncologists to keep up with the rapidly growing volume and breadth of information, especially those that describe therapeutic implications of biomarkers and therefore relevant for treatment selection. In an effort to improve and speed up the process of manually reviewing and extracting relevant information from literature, we have developed a natural language processing (NLP)-based text mining (TM) system called eGARD (extracting Genomic Anomalies association with Response to Drugs). This system relies on the syntactic nature of sentences coupled with various textual features to extract relations between genomic anomalies and drug response from MEDLINE abstracts. Our system achieved high precision, recall and F-measure of up to 0.95, 0.86 and 0.90, respectively, on annotated evaluation datasets created in-house and obtained externally from PharmGKB. Additionally, the system extracted information that helps determine the confidence level of extraction to support prioritization of curation. Such a system will enable clinical researchers to explore the use of published markers to stratify patients upfront for best-fit therapies and readily generate hypotheses for new clinical trials.

bioinformatics↗

bioRxiv2017

EXPLANe: An Extensible Framework for Poster Annotation with Mobile Devices

SummaryScientific posters tend to be brief, unstructured, and generally unsuitable for communication beyond a poster session. This paper describes EXPLANe, a framework for annotating posters using optical text recognition and web services on mobile devices. EXPLANe is demonstrated through an interface to the MyVariant.info variant annotation web services, and provides users a list of biological information linked with genetic variants (as found via extracted RSIDs from annotated posters). This paper delineates the architecture of the application, and includes results of a five-part evaluation we conducted. Researchers and developers can use the existing codebase as a foundation from which to generate their own annotation tabs when analyzing and annotating posters.\n\nAvailabilityAlpha EXPLANe software is available as an open source application at https://github.com/ngopal/EXPLANe\n\nContactSean D. Mooney (sdmooney@uw.edu)

scientific communication and education↗

bioRxiv2017

STAR-Fusion: Fast and Accurate Fusion Transcript Detection from RNA-Seq

MotivationFusion genes created by genomic rearrangements can be potent drivers of tumorigenesis. However, accurate identification of functionally fusion genes from genomic sequencing requires whole genome sequencing, since exonic sequencing alone is often insufficient. Transcriptome sequencing provides a direct, highly effective alternative for capturing molecular evidence of expressed fusions in the precision medicine pipeline, but current methods tend to be inefficient or insufficiently accurate, lacking in sensitivity or predicting large numbers of false positives. Here, we describe STAR-Fusion, a method that is both fast and accurate in identifying fusion transcripts from RNA-Seq data.\n\nResultsWe benchmarked STAR-Fusions fusion detection accuracy using both simulated and genuine Illumina paired-end RNA-Seq data, and show that it has superior performance compared to popular alternative fusion detection methods.\n\nAvailability and implementationSTAR-Fusion is implemented in Perl, freely available as open source software at http://star-fusion.github.io, and supported on Linux.\n\nContactbhaas@broadinstitute.org

bioinformatics↗

bioRxiv2017

A Novel And Efficient Algorithm For De Novo Discovery Of Mutated Driver Pathways In Cancer

Next-generation sequencing studies on cancer somatic mutations have discovered that driver mutations tend to appear in most tumor samples, but they barely overlap in any single tumor sample, presumably because a single driver mutation can perturb the whole pathway. Based on the corresponding new concepts of coverage and mutual exclusivity, new methods can be designed for de novo discovery of mutated driver pathways in cancer. Since the computational problem is a combinatorial optimization with an objective function involving a discontinuous indicator function in high dimension, many existing optimization algorithms, such as a brute force enumeration, gradient descent and Newton's methods, are practically infeasible or directly inapplicable. We develop a new algorithm based on a novel formulation of the problem as non-convex programming and nonconvex regularization. The method is computationally more efficient, effective and scalable than existing Monte Carlo searching and several other algorithms, which have been applied to The Cancer Genome Atlas (TCGA) project. We also extend the new method for integrative analysis of both mutation and gene expression data. We demonstrate the promising performance of the new methods with applications to three cancer datasets to discover de novo mutated driver pathways.

bioinformatics↗

bioRxiv2016

Chimeric Genes Revealed in the Polyploidy Fish Hybrids of Carassius cuvieri (Female) x Megalobrama amblycephala (Male)

The genomes of newly formed natural or artificial polyploids may experience rapid gene loss and genome restructuring. In this study, we obtained tetraploid hybrids (4n=148, 4nJB) and triploid hybrids (3n=124, 3nJB) derived from the hybridization of two different subfamily species Carassius cuvieri ([female], 2n = 100, JCC) and Megalobrama amblycephala ([male], 2n = 48, BSB). Some significant morphological and physiological differences were detected in the polyploidy hybrids compared with their parents. To reveal the molecular traits of the polyploids, we compared the liver transcriptomes of 4nJB, 3nJB and their parents. The results indicated high proportion chimeric genes (31 > %) and mutated orthologous genes (17 > %) both in 4nJB and 3nJB. We classified 10 gene patterns within three categories in 4nJB and 3nJB orthologous gene, and characterized 30 randomly chosen genes using genomic DNA to confirm the chimera or mutant. Moreover, we mapped chimeric genes involved pathways and discussed that the phenotypic novelty of the hybrids may relate to some chimeric genes. For example, we found there is an intragenic insertion in the K+ channel kcnk5b, which may be related to the novel presence of the barbels in 4nJB. Our results indicated that the genomes of newly formed polyploids experienced rapid restructuring post-polyploidization, which may results in the phenotypic and phenotypic changes among the polyploidy hybrid offspring. The formation of the 4nJB and 3nJB provided new insights into the genotypic and phenotypic diversity of hybrid fish resulting from distant hybridization between subfamilies.

developmental biology↗