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Khan, R. R.

Publications and source records attributed to Khan, R. R..

4 recordsLinked to original sources

Identification of Sample Processing Errors in Microbiome Studies Using Host Genetic Profiles

In microbiome studies, sample processing errors are frequent and difficult to detect, especially in large studies involving multiple sites, personnel, and sample types. We present two complementary approaches to identify such errors using host DNA profiled via metagenomic sequencing of microbiome samples. The first approach compares host SNPs inferred from metagenomics to independently obtained genotypes (e.g., microarray genotypes) to match samples to their donors, while the second method compares metagenomics-inferred SNPs between samples to identify samples supplied by the same donor. Furthermore, we demonstrate that combining these methods with experimental metadata provides greater confidence in the identification of errors. Analyzing a longitudinal vaginal microbiome dataset, we demonstrate the ability of our approach to identify mislabeled samples. Using subsampling, we further show that our methods are robust to low sequencing coverage. Overall, our analysis highlights the frequency of processing errors in microbiome studies. We therefore recommend applying error-detection methods in all studies with suitable data.

bioinformatics↗

Phenotypic and genotypic detection of the virulence factors and their association with antibiotic resistance in Enterococcus species

Abstract- Along with the emergence of drug resistant Enterococcal infection, role of various virulence factors in Enterococci is an emerging concept. A number of virulence factors like biofilm formation, hemolysin production, gelatin hydrolysis have important role in the pathogenesis of Enterococci and also associated with antibiotic resistance. The aim of our study was to detect the virulence factors and their encoding genes (asa, gelE, esp, ebpR, hyl gene for biofilm; cylA gene for hemolysis; gelE gene for gelatin hydrolysis) and also observe their association with antimicrobial resistance Enterococci. A total of 87 Enterococci were collected from different clinical samples. Virulence factors were detected phenotypically and antibiotic sensivity were done by Kirby Bauer disc diffusion method. Virulence genes were detected by conventional multiplex PCR and only the ebpR gene was detected by single conventional PCR. Majority of the isolated Enterococci were E. faecalis (75%) followed by E. faecium (23%) and (2%) E. raffinosus were also detected. About 52.3% of E. faecalis and 35% of E. faecium isolates were biofilm producers. Significant association was found between biofilm formation and asa, esp, ebpR genes both in E. faecalis and in E. faecium. Hemolysis was observed phenotypically in 30.8% isolates of E. faecalis and 20% isolates of E. faecium. Significant association was observed between cylA gene and hemolysin production in E. faecalis. Antibiotic resistance were higher in biofilm and hemolysin producing isolates of both species. Resistance to some antibiotics including ampicillin, ciprofloxacin, gentamicin were significantly higher among biofilm and hemolysin producer in E. faecalis.

microbiology↗

Uncovering a neural circuit controlling adult quiescent neural stem cell activation in the subventricular zone

Neurogenesis and differentiation of the neural stem cells (NSCs) in the subventricular zone (SVZ) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. Here we identified a novel circuit that regulates neurogenesis and cellular proliferation in the lateral ventricle SVZ (LV-SVZ). Our results demonstrate direct glutamatergic inputs from the frontal cortex as well as local inhibitory interneurons, control the activity of distinctive cholinergic neurons in the subependymal zone (subep-ChAT+). In vivo optogenetic stimulation and inhibition in this circuit were sufficient to control local SVZ neurogenesis, LV NSCs proliferation, and SVZ cellular divisions in ventral SVZ. These findings shed light on local and distal neural circuit activity-dependent regulation of postnatal and adult SVZ neurogenesis and LV-SVZ cellular proliferation.

neuroscience↗

Genetic variation in CSMD1 affects amygdala connectivity and prosocial behavior

The amygdala is one of the most widely connected structures in the primate brain and plays a key role in social and emotional behavior. Here, we present the first genome-wide association study (GWAS) of whole-brain resting-state amygdala networks to discern whether connectivity in these networks could serve as an endophenotype for social behavior. Leveraging published resting-state amygdala networks as a priori endophenotypes in a GWAS meta-analysis of two adolescent cohorts, we identified a common polymorphism on chr.8p23.2 (rs10105357 A/G, MAF (G)=0.35) associated with stronger connectivity in the medial amygdala network (beta=0.20, p=2.97x10-8). This network contains regions that support reward processes and affiliative behavior. People carrying two copies of the minor allele for rs10105357 participate in more prosocial behaviors (t=2.644, p=0.008) and have higher CSMD1 expression in the temporal cortex (t=3.281, p=0.002) than people with one or no copy of the allele. In post-mortem brains across the lifespan, we found that CSMD1 expression is relatively high in the amygdala (2.79 fold higher than white matter, p=1.80x10-29), particularly so for nuclei in the medial amygdala, reaching a maximum in later stages of development. Amygdala network endophenotyping has the potential to accelerate genetic discovery in disorders of social function, such as autism, in which CSMD1 may serve as a diagnostic and therapeutic target.

neuroscience↗