bioRxiv Science⌕ Search

Biology subjects

Chan, L. S.

Publications and source records attributed to Chan, L. S..

3 recordsLinked to original sources

Zero is not absence: censoring-based differential abundance analysis for microbiome data

Microbiome data analysis faces the challenge of sparsity, with many entries recorded as zeros. In differential abundance analysis, the presence of excessive zeros in data violates distributional assumptions and creates ties, leading to an increased risk of type I errors and reduced statistical power. To address this, we developed a novel normalization method, called CAMP, for microbiome data by treating zeros as censored observations, transforming raw read counts into tie-free time-to-event-like data. This enables the use of survival analysis techniques, like the Cox proportional hazards model, for differential abundance analysis. Extensive simulations demonstrate that CAMP achieves proper type I error control and high power. Applying CAMP to a human gut microbiome dataset, we identify 60 new differentially abundant taxa across geographic locations, showcasing its usefulness. CAMP over-comes sparsity challenges, enabling improved statistical analysis and providing valuable insights into microbiome data in various contexts.

microbiology↗

DrFARM: Identification and inference for pleiotropic gene in GWAS

In a standard analysis, pleiotropic variants are identified by running separate genome-wide association studies (GWAS) and combining results across traits. But such two-stage statistical approach may lead to spurious results. We propose a new statistical approach, Debiased-regularized Factor Analysis Regression Model (DrFARM), through a joint regression model for simultaneous analysis of high-dimensional genetic variants and multilevel dependencies. This joint modeling strategy controls overall error to permit universal false discovery rate (FDR) control. DrFARM uses the strengths of the debiasing technique and the Cauchy combination test, both being theoretically justified, to establish a valid post selection inference on pleiotropic variants. Through extensive simulations, we show that DrFARM appropriately controls overall FDR. Applying DrFARM to data on 1,031 metabolites measured on 6,135 men from the Metabolic Syndrome in Men (METSIM) study, we identify 288 new metabolite associations at loci that did not reach statistical significance in prior METSIM metabolite GWAS.

genomics↗

The urinary microbiome associated with bladder cancer

Recent findings suggest that microorganisms inhabiting the human body can influence the development of cancer, but the role of microorganisms in bladder cancer pathogenesis has not been explored yet. The aim of this study was to characterize and compare the urinary microbiome of bladder cancer patients with those of healthy controls. Bacterial communities present in urine specimens collected from male patients diagnosed with primary or recurrent, non-muscle invasive bladder cancers, and from healthy, age-matched individuals were analysed using 16S Illumina MiSeq sequencing. Our result show that the most abundant phylum in both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and Proteobacteria. While microbial diversity and overall microbiome composition were not significantly different between bladder cancer and healthy samples, we identified specific operational taxonomic units (OTUs) that were significantly more abundant (p < 0.05) in either type of samples. Among those that were significantly enriched in the bladder cancer group, we identified an OTU belonging to genus Fusobacterium, a possible protumorigenic pathogen. Three OTUs more abundant in healthy urines were from genera Veillonella, Streptococcus and Corynebacterium. Detected microbiome changes suggest that microbiome may be a factor in bladder cancer pathology, and the clinical implications of reported results remain to be explored.

cancer biology↗