Biology subjects

Yao, C.

Publications and source records attributed to Yao, C..

76 records · Page 5Linked to original sources

bioRxiv2018

Network-Based Biomarkers Enable Cross-Disease Biomarker Discovery

Biomarkers lie at the heart of precision medicine, biodiversity monitoring, agricultural pathogen detection, amongst others. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers almost always involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molecular models that robustly predict key phenotypes. We therefore created SIMMS: an algorithm that fragments pathways into functional modules and uses these to predict phenotypes. We applied SIMMS to multiple data-types across four diseases, and in each it reproducibly identified subtypes, made superior predictions to the best bespoke approaches, and identified known and novel signaling nodes. To demonstrate its ability on a new dataset, we measured 33 genes/nodes of the PIK3CA pathway in 1,734 FFPE breast tumours and created a four-subnetwork prediction model. This model significantly out-performed existing clinically-used molecular tests in an independent 1,742-patient validation cohort. SIMMS is generic and can work with any molecular data or biological network, and is freely available at: https://cran.r-project.org/web/packages/SIMMS.

bioinformatics↗

bioRxiv2017

MicroRNA-21 Regulates Metabolic Adaptation of Pathogenic TH17 cells and Controls Autoimmune Inflammation

TH17 cells exhibit great heterogeneity and variable functional states in vivo. However, metabolic reprogramming of TH17 cells in vivo and its regulation during autoimmunity and host defence is unknown. Here we report that TH17 cells derived in vivo show discrete metabolic states. Metabolic states of TH17 cells in vivo were controlled at the epigenetic level, with conserved regulatory region of key metabolic regulators show distinct chromatin accessibility as demonstrated by chromatin landscape profiling. TGF-{beta}1 signaling was further shown to be crucial for remodeling of TH17 cell chromatin states, Ahr and miR-21 were identified as essential metabolic regulators for TH17 cells. Understanding metabolic reprogramming of TH17 cells in vivo may therefore provide more defined therapeutic intervention to TH17 cell mediated autoimmune diseases and insights into TH17 cell mediated host defence.

immunology↗

bioRxiv2017

Genome-wide Association Study Of Plasma Proteins Identifies Putatively Causal Genes, Proteins, And Pathways For Cardiovascular Disease

Identifying genetic variants associated with circulating protein concentrations (pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteomes causal role in disease and bridge a GWAS knowledge gap for hitherto unexplained SNP-disease associations. We conducted GWAS of 71 high-value proteins for cardiovascular disease in 6,861 Framingham Heart Study participants followed by external replication. We comprehensively mapped thousands of pQTLs, including functional annotations and clinical-trait associations, and created an integrated plasma-protein-QTL searchable database. We next identified 15 proteins with pQTLs coinciding with coronary heart disease (CHD)-related variants from GWAS or tested causal for CHD by Mendelian randomization; most of these proteins were associated with new-onset cardiovascular disease events in Framingham participants with long-term follow-up. Identifying pQTLs and integrating them with GWAS results yields insights into genes, proteins, and pathways that may be causally associated with disease and can serve as therapeutic targets for treatment and prevention.

epidemiology↗

bioRxiv2017

Regulation Of Iron Homeostasis By SPAK-Dependent Modulation Of FBXL5 Stability

Intracellular iron homeostasis is regulated by a proteolytic switch whereby the E3 ubiquitin ligase FBXL5 targets iron regulatory proteins (IRPs) for ubiquitin-dependent degradation in iron-replete conditions while it is itself degraded during iron deficiency allowing IRPs to accumulate and regulate their downstream RNA targets. The cellular pathways that control FBXL5 degradation in low iron conditions are not well understood. Here, we report the identification of the STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) as a novel regulator of FBXL5 stability. We find that SPAK, a kinase previously implicated in osmotic stress regulation, regulates intracellular iron homeostasis through its physical association with FBXL5. This role is dependent on its kinase activity as overexpression of constitutively active SPAK increases FBXL5 poly-ubiquitination and degradation. Through this work, we have discovered a novel role for SPAK that extends beyond its well-established function in salt homeostasis and raises the possibility for signaling crosstalk between iron homeostatic and osmotic regulatory pathways.

biochemistry↗