Biology subjects

Fan, D.

Publications and source records attributed to Fan, D..

3 recordsLinked to original sources

bioRxiv2018

Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis

Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Pleckstrin homology domain-containing family O member 1 (PLEKHO1) was previously identified as a negative regulator of osteogenic lineage activity. Here we demonstrated that PLEKHO1 was highly expressed in osteoblasts of articular specimens from RA patients and inflammatory arthritis mice. Genetic deletion of osteoblastic Plekho1 ameliorated joint inflammation in mice with collagen-induced arthritis (CIA) and K/BxN serum-transfer arthritis (STA), whereas overexpressing Plekho1 only within osteoblasts in CIA and STA mice demonstrated exacerbated local inflammation. Further in vitro studies indicated that PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-kB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition improved joint inflammation and attenuated bone formation reduction in CIA mice and non-human primate arthritis model. These data strongly suggest that highly expressed PLEKHO1 in osteoblast mediates joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA.

cell biology↗

bioRxiv2018

Improved prediction of chronological age from DNA methylation limits it as a biomarker of ageing

DNA methylation is associated with age. The deviation of age predicted from DNA methylation from actual age has been proposed as a biomarker for ageing. However, a better prediction of chronological age implies less opportunity for biological age. Here we used 13,661 samples (from blood and saliva) in the age range of 2 to 104 years from 14 cohorts measured on Illumina HumanMethylation450/EPIC arrays to perform prediction analyses. We show that increasing the sample size achieves a smaller prediction error and higher correlations in test datasets. We demonstrate that smaller prediction errors provide a limit to how much variation in biological ageing can be captured by methylation and provide evidence that age predictors from small samples are prone to confounding by cell composition. Our predictor shows a similar or better performance in non-blood tissues including saliva, endometrium, breast, liver, adipose and muscle, compared with Horvaths across-tissue age predictor.

bioinformatics↗

bioRxiv2017

UBiT2: a client-side web-application for gene expression data analysis

We present a purely client-side web-application, UBiT2 (User-friendly BioInformatics Tools), that provides installation-free, offline alignment, analysis, and visualization of RNA-sequencing as well as qPCR data. Analysis modules were designed with single cell transcriptomic analysis in mind. Using just a browser, users can perform standard analyses such as quality control, filtering, hierarchical clustering, principal component analysis, differential expression analysis, gene set enrichment testing, and more, all with interactive visualizations and exportable publication-quality figures. We apply UBiT2 to recapitulate findings from single cell RNA-seq and Fluidigm Biomark multiplex RT-qPCR gene expression datasets. UBiT2 is available at http://pklab.med.harvard.edu/jean/ubit2/index.html with open-source code available at https://github.com/JEFworks/ubit2.

bioinformatics↗