Quan Zhou

Bio: Quan Zhou is an academic researcher from Texas A&M University. The author has contributed to research in topics: Mathematics & Asymptotic distribution. The author has an hindex of 7, co-authored 32 publications receiving 389 citations. Previous affiliations of Quan Zhou include Rice University & Agricultural Research Service.

Coverage evaluation of universal bacterial primers using the metagenomic datasets

Abstract: Background The coverage of universal primers for the bacterial 16S rRNA gene plays a crucial role in the correct understanding of microbial community structure. However, existing studies on primer coverage are limited by the lack of appropriate databases and are restricted to the domain level. Additionally, most studies do not account for the positional effect of single primer-template mismatches. In this study, we used 7 metagenomic datasets as well as the Ribosomal Database Project (RDP) to assess the coverage of 8 widely used bacterial primers.

Postnatal epigenetic regulation of intestinal stem cells requires DNA methylation and is guided by the microbiome

Abstract: DNA methylation is an epigenetic mechanism central to development and maintenance of complex mammalian tissues, but our understanding of its role in intestinal development is limited. We use whole genome bisulfite sequencing, and find that differentiation of mouse colonic intestinal stem cells to intestinal epithelium is not associated with major changes in DNA methylation. However, we detect extensive dynamic epigenetic changes in intestinal stem cells and their progeny during the suckling period, suggesting postnatal epigenetic development in this stem cell population. We find that postnatal DNA methylation increases at 3′ CpG islands (CGIs) correlate with transcriptional activation of glycosylation genes responsible for intestinal maturation. To directly test whether 3′ CGI methylation regulates transcription, we conditionally disrupted two major DNA methyltransferases, Dnmt1 or Dnmt3a, in fetal and adult intestine. Deficiency of Dnmt1 causes severe intestinal abnormalities in neonates and disrupts crypt homeostasis in adults, whereas Dnmt3a loss was compatible with intestinal development. These studies reveal that 3′ CGI methylation is functionally involved in the regulation of transcriptional activation in vivo, and that Dnmt1 is a critical regulator of postnatal epigenetic changes in intestinal stem cells. Finally, we show that postnatal 3′ CGI methylation and associated gene activation in intestinal epithelial cells are significantly altered by germ-free conditions. Our results demonstrate that the suckling period is critical for epigenetic development of intestinal stem cells, with potential important implications for lifelong gut health, and that the gut microbiome guides and/or facilitates these postnatal epigenetic processes.

Strong Selection at MHC in Mexicans since Admixture

Abstract: Mexicans are a recent admixture of Amerindians, Europeans, and Africans. We performed local ancestry analysis of Mexican samples from two genome-wide association studies obtained from dbGaP, and discovered that at the MHC region Mexicans have excessive African ancestral alleles compared to the rest of the genome, which is the hallmark of recent selection for admixed samples. The estimated selection coefficients are 0.05 and 0.07 for two datasets, which put our finding among the strongest known selections observed in humans, namely, lactase selection in northern Europeans and sickle-cell trait in Africans. Using inaccurate Amerindian training samples was a major concern for the credibility of previously reported selection signals in Latinos. Taking advantage of the flexibility of our statistical model, we devised a model fitting technique that can learn Amerindian ancestral haplotype from the admixed samples, which allows us to infer local ancestries for Mexicans using only European and African training samples. The strong selection signal at the MHC remains without Amerindian training samples. Finally, we note that medical history studies suggest such a strong selection at MHC is plausible in Mexicans.

Sequential rerandomization.

Abstract: The seminal work of Morgan and Rubin (2012) considers rerandomization for all the units at one time. In practice, however, experimenters may have to rerandomize units sequentially. For example, a clinician studying a rare disease may be unable to wait to perform an experiment until all the experimental units are recruited. Our work offers a mathematical framework for sequential rerandomization designs, where the experimental units are enrolled in groups. We formulate an adaptive rerandomization procedure for balancing treatment/control assignments over some continuous or binary covariates, using Mahalanobis distance as the imbalance measure. We prove in our key result, Theorem 3, that given the same number of rerandomizations (in expected value), under certain mild assumptions, sequential rerandomization achieves better covariate balance than rerandomization at one time.

On the Null Distribution of Bayes Factors in Linear Regression

Abstract: We show that under the null, the 2log (Bayesfactor) is asymptotically distributed as a weighted sum of chi-squared random variables with a shifted mean. This claim holds for Bayesian multi-linear regression with a family of conjugate priors, namely, the normal-inverse-gamma prior, the g-prior, and the normal prior. Our results have three immediate impacts. First, we can compute analytically a p-value associated with a Bayes factor without the need of permutation. We provide a software package that can evaluate the p-value associated with Bayes factor efficiently and accurately. Second, the null distribution is illuminating to some intrinsic properties of Bayes factor, namely, how Bayes factor quantitatively depends on prior and the genesis of Bartlett's paradox. Third, enlightened by the null distribution of Bayes factor, we formulate a novel scaled Bayes factor that depends less on the prior and is immune to Bartlett's paradox. When two tests have an identical p-value, the test with a larger powe...

Minor revision to V4 region SSU rRNA 806R gene primer greatly increases detection of SAR11 bacterioplankton

Abstract: High-throughput sequencing of small subunit ribosomal RNA (SSU rRNA) genes from marine environments is a widely applied method used to uncover the composition of micro- bial communities. We conducted an analysis of surface ocean waters with the commonly employed hypervariable 4 region SSU rRNA gene primers 515F and 806R, and found that bacteria belonging to the SAR11 clade of Alphaproteobacteria, a group typically making up 20 to 40% of the bacterioplankton in this environment, were greatly underrepresented and comprised <4% of the total community. Using the SILVA reference database, we found a single nucleotide mismatch to nearly all SAR11 subclades, and revised the 806R primer so that it increased the detection of SAR11 clade sequences in the database from 2.6 to 96.7%. We then compared the performance of the original and revised 806R primers in surface seawater samples, and found that SAR11 com- prised 0.3 to 3.9% of sequences with the original primers and 17.5 to 30.5% of the sequences with the revised 806R primer. Furthermore, an investigation of seawater obtained from aquaria re - vealed that SAR11 sequences acquired with the revised 806R primer were more similar to natural cellular abundances of SAR11 detected using fluorescence in situ hybridization counts. Collectively, these results demonstrate that a minor adjustment to the 806R primer will greatly increase detec- tion of the globally abundant SAR11 clade in marine and lake environments, and enable inclusion of this important bacterial lineage in experimental and environmental-based studies.

Sampling and Bayes' inference in scientific modelling and robustness

Abstract: : Scientific learning is an iterative process employing Criticism and Estimation. Correspondingly the formulated model factors into two complimentary parts - a predictive part allowing model criticism, and a Bayes posterior part allowing estimation. Implications for significance tests, the theory of precise measurement, and for ridge estimates are considered. Predictive checking functions for transformation, serial correlation, bad values, and their relation with Bayesian options are considered. Robustness is seen from a Bayesian viewpoint and examples are given. For the bad value problem a comparison with M estimators is made. (Author)

The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients?

Abstract: The gut microbiota is emerging as a promising target for the management or prevention of inflammatory and metabolic disorders in humans. Many of the current research efforts are focused on the identification of specific microbial signatures, more particularly for those associated with obesity, type 2 diabetes, and cardiovascular diseases. Some studies have described that the gut microbiota of obese animals and humans exhibits a higher Firmicutes/Bacteroidetes ratio compared with normal-weight individuals, proposing this ratio as an eventual biomarker. Accordingly, the Firmicutes/Bacteroidetes ratio is frequently cited in the scientific literature as a hallmark of obesity. The aim of the present review was to discuss the validity of this potential marker, based on the great amount of contradictory results reported in the literature. Such discrepancies might be explained by the existence of interpretative bias generated by methodological differences in sample processing and DNA sequence analysis, or by the generally poor characterization of the recruited subjects and, more particularly, the lack of consideration of lifestyle-associated factors known to affect microbiota composition and/or diversity. For these reasons, it is currently difficult to associate the Firmicutes/Bacteroidetes ratio with a determined health status and more specifically to consider it as a hallmark of obesity.

Tales from the crypt: new insights into intestinal stem cells.

Abstract: The intestinal epithelium withstands continuous mechanical, chemical and biological insults despite its single-layered, simple epithelial structure. The crypt-villus tissue architecture in combination with rapid cell turnover enables the intestine to act both as a barrier and as the primary site of nutrient uptake. Constant tissue replenishment is fuelled by continuously dividing stem cells that reside at the bottom of crypts. These cells are nurtured and protected by specialized epithelial and mesenchymal cells, and together constitute the intestinal stem cell niche. Intestinal stem cells and early progenitor cells compete for limited niche space and, therefore, the ability to retain or regain stemness. Those cells unable to do so differentiate to one of six different mature cell types and move upwards towards the villus, where they are shed into the intestinal lumen after 3-5 days. In this Review, we discuss the signals, cell types and mechanisms that control homeostasis and regeneration in the intestinal epithelium. We investigate how the niche protects and instructs intestinal stem cells, which processes drive differentiation of mature cells and how imbalance in key signalling pathways can cause human disease.