Biology subjects

Fan, C.

Publications and source records attributed to Fan, C..

113 records · Page 7Linked to original sources

bioRxiv2019

PRISM: a comprehensive 3D structure database for post-translational modifications and mutations with functional impact

Post-translational modifications (PTMs) play very important roles in various cell signalling pathways and biological process. Due to PTMs extremely important roles, many major PTMs have been thoroughly studied, while the functional and mechanical characterization of major PTMs is well-documented in several databases. However, most currently available databases mainly focus on protein sequences, while the real 3D structures of PTMs have been largely ignored. Therefore, studies of PTMs 3D structural signatures have been severely limited by the deficiency of the data. Here, we develop PRISMOID, a novel publicly available and free 3D structure database for a wide range of PTMs. PRISMOID represents an up-to-date and interactive online knowledge base with specific focus on 3D structural contexts of PTMs sites and mutations that occur on PTMs and in the close proximity of PTM sites with functional impact. The first version of PRISMOID encompasses 17,145 non-redundant modification sites on 3,919 related protein 3D structure entries pertaining to 37 different types of PTMs. Our entry web page is organized in a comprehensive manner, including detailed PTM annotation on the 3D structure and biological information in terms of mutations affecting PTMs, secondary structure features and per-residue solvent accessibility features of PTM sites, domain context, predicted natively disordered regions and sequence alignments. In addition, high-definition JavaScript packages are employed to enhance information visualization in PRISMOID. PRISMOID equips a variety of interactive and customizable search options and data browsing functions; these capabilities allow users to access data via keyword, ID, and advanced options combination search in an efficient and user-friendly way. A download page is also provided to enable users to download the SQL file, computational structural features, and PTM sites data. We anticipate PRISMOID will swiftly become an invaluable online resource, assisting both biologists and bioinformaticians to conduct experiments and develop applications supporting discovery efforts in the sequence-structural-functional relationship of PTMs and providing important insight into mutations and PTM sites interaction mechanisms. The PRISMOID database is freely accessible at http://prismoid.erc.monash.edu/. The database and web interface are implemented in MySQL, JSP, JavaScript, and HTML with all major browsers supported.

bioinformatics↗

bioRxiv2018

Lin28B is involved in curcumin-reversed paclitaxel chemoresistance and associated with poor prognosis in hepatocellular carcinoma

Chemoresistance remains a big challenge in hepatocellular carcinoma (HCC) treatment. Several studies indicated that RNA-binding protein Lin28B serves an oncogenic role in HCC, but its activity in HCC chemotherapy has never been assessed. In this study, we found that overexpression of Lin28B significantly increased the paclitaxel chemoresistance in two different HCC cells lines while silencing Lin28B reduced the chemoresistance in paclitaxel-resistance HCC cells. Curcumin, a natural anti-cancer agent, increased the sensitivity of HCC cells to paclitaxel through inhibiting NF-{kappa}B stimulated Lin28B expression both in vitro and in vivo. Furthermore, by analyzing TCGA (The Cancer Genome Atlas) LIHC (liver hepatocellular carcinoma) and GSE14520 databases, we found that Lin28B was highly up-regulated in HCC tissue compared with that in normal tissue and associated with -fetoprotein levels, and that patients with Lin28B higher expression had a significant shorter overall survival time than those with Lin28B lower expression. Our data reveal that Lin28B may serve as a predictive biomarker and a treatment target to reverse HCC chemotherapy resistance in future clinical practice.\n\nSummary statementupregulation of Lin28B not only confers poor prognosis in HCC patients but also increases chemoresistance in HCC cells. Thus, Lin28B may serve as a predictive biomarker for use to reverse chemoresistance in clinical practice.

cell biology↗

bioRxiv2018

An Integrative Boosting Approach for Predicting Survival Time With Multiple Genomics Platforms

Recent technological advances have made it possible to collect multiple types of genomics data on the same set of patients. It is of great interest to integrate multiple genomics data types together for predicting disease outcomes. We propose a variable selection method, termed Integrative Boosting (I-Boost), that makes proper use of all available clinical and genomics data in predicting individual patient survival time. Through simulation studies and applications to data sets from The Cancer Genome Atlas, we demonstrate that I-Boost provides substantially higher prediction accuracy than existing variable selection methods. Using I-Boost, we show that (1) the integration of multiple genomics platforms with clinical variables significantly improves the prediction accuracy for survival time over the use of clinical variables alone; (2) gene expression values are typically more prognostic of survival time than other genomics data types; and (3) gene modules/signatures are at least as prognostic as the collection of individual gene expression data.

bioinformatics↗

bioRxiv2018

Structure of the human lipid-sensitive cation channel TRPC3

The TRPC channels are crucially involved in store-operated calcium entry and calcium homeostasis, and they are thus implicated in human diseases such as neurodegenerative disease, cardiac hypertrophy, and spinocerebellar ataxia. We present structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has an acorn-like shape with four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism. The third transmembrane helix S3 is remarkably long, resulting in a windmill-like transmembrane domain, and constituting an extracellular domain that may serve as a sensor of external stimuli. We identified two lipid binding sites, one being sandwiched between the pre-S1 elbow and the S4-S5 linker, and the other being close to the ion-conducting pore, where the conserved LWF motif of the TRPC family is located.

biophysics↗

bioRxiv2017

Semi-Parametric Covariate-Modulated Local False Discovery Rate For Genome-Wide Association Studies

While genome-wide association studies (GWAS) have discovered thousands of risk loci for heritable disorders, so far even very large meta-analyses have recovered only a fraction of the heritability of most complex traits. Recent work utilizing variance components models has demonstrated that a larger fraction of the heritability of complex phenotypes is captured by the additive effects of SNPs than is evident only in loci surpassing genome-wide significance thresholds, typically set at a Bonferroni-inspired p [≤] 5 x 10-8. Procedures that control false discovery rate can be more powerful, yet these are still under-powered to detect the majority of non-null effects from GWAS. The current work proposes a novel Bayesian semi-parametric two-group mixture model and develops a Markov Chain Monte Carlo (MCMC) algorithm for a covariate-modulated local false discovery rate (cmfdr). The probability of being non-null depends on a set of covariates via a logistic function, and the non-null distribution is approximated as a linear combination of B-spline densities, where the weight of each B-spline density depends on a multinomial function of the covariates. The proposed methods were motivated by work on a large meta-analysis of schizophrenia GWAS performed by the Psychiatric Genetics Consortium (PGC). We show that the new cmfdr model fits the PGC schizophrenia GWAS test statistics well, performing better than our previously proposed parametric gamma model for estimating the non-null density and substantially improving power over usual fdr. Using loci declared significant at cmfdr [≤] 0.20, we perform follow-up pathway analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) homo sapiens pathways database. We demonstrate that the increased yield from the cmfdr model results in an improved ability to test for pathways associated with schizophrenia compared to using those SNPs selected according to usual fdr.

bioinformatics↗