Honors & Awards
Global Health Equity Scholar, NIH Fogarty and Stanford Center for Innovation in Global Health (July 2023-present)
Gerald J. Lieberman Fellowship, Stanford VPGE (2022-2023)
Stanford Graduate Fellowship, Stanford VPGE (2018-2021)
Boards, Advisory Committees, Professional Organizations
Global Health Postdoctoral Affiliate, Stanford University Center for Innovation in Global Health (2023 - Present)
Ami Bhatt, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
I am currently a Global Health Equity Scholar supported by the NIH Fogarty International Center. I am conducting my fellowship year at the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at the University of the Witwatersrand in Johannesburg, South Africa under the mentorship of Ami Bhatt, MD, PhD and Scott Hazelhurst MSc PhD. My research focuses on identifying genomic, microbiome, and clinical risk factors associated with the development of HIV-related comorbidities.
Quantifying bias introduced by sample collection in relative and absolute microbiome measurements.
To gain insight into the accuracy of microbial measurements, it is important to evaluate sources of bias related to sample condition, preservative method and bioinformatic analyses. There is increasing evidence that measurement of the total count and concentration of microbes in the gut, or 'absolute abundance', provides a richer source of information than relative abundance and can correct some conclusions drawn from relative abundance data. However, little is known about how preservative choice can affect these measurements. In this study, we investigated how two common preservatives and short-term storage conditions impact relative and absolute microbial measurements. OMNIgene GUT OMR-200 yields lower metagenomic taxonomic variation between different storage temperatures, whereas Zymo DNA/RNA Shield yields lower metatranscriptomic taxonomic variation. Absolute abundance quantification reveals two different causes of variable Bacteroidetes:Firmicutes ratios across preservatives. Based on these results, we recommend OMNIgene GUT OMR-200 preservative for field studies and Zymo DNA/RNA Shield for metatranscriptomics studies, and we strongly encourage absolute quantification for microbial measurements.
View details for DOI 10.1038/s41587-023-01754-3
View details for PubMedID 37106038
View details for PubMedCentralID 5069758
Short- and long-read metagenomics of urban and rural South African gut microbiomes reveal a transitional composition and undescribed taxa.
2022; 13 (1): 926
Human gut microbiome research focuses on populations living in high-income countries and to a lesser extent, non-urban agriculturalist and hunter-gatherer societies. The scarcity of research between these extremes limits our understanding of how the gut microbiota relates to health and disease in the majority of the world's population. Here, we evaluate gut microbiome composition in transitioning South African populations using short- and long-read sequencing. We analyze stool from adult females living in rural Bushbuckridge (n=118) or urban Soweto (n=51) and find that these microbiomes are taxonomically intermediate between those of individuals living in high-income countries and traditional communities. We demonstrate that reference collections are incomplete for characterizing microbiomes of individuals living outside high-income countries, yielding artificially low beta diversity measurements, and generate complete genomes of undescribed taxa, including Treponema, Lentisphaerae, and Succinatimonas. Our results suggest that the gut microbiome of South Africans does not conform to a simple "western-nonwestern" axis andcontains undescribed microbial diversity.
View details for DOI 10.1038/s41467-021-27917-x
View details for PubMedID 35194028
Genetic determinants of EGFR-Driven Lung Cancer Growth and Therapeutic Response In Vivo.
In lung adenocarcinoma, oncogenic EGFR mutations co-occur with many tumor suppressor gene alterations, however the extent to which these contribute to tumor growth and response to therapy in vivo remains largely unknown. By quantifying the effects of inactivating ten putative tumor suppressor genes in a mouse model of EGFR-driven Trp53-deficient lung adenocarcinoma, we found that Apc, Rb1, or Rbm10 inactivation strongly promoted tumor growth. Unexpectedly, inactivation of Lkb1 or Setd2 - the strongest drivers of growth in a Kras-driven model - reduced EGFR-driven tumor growth. These results are consistent with mutational frequencies in human EGFR- and KRAS-driven lung adenocarcinomas. Furthermore, Keap1 inactivation reduced the sensitivity of EGFR-driven tumors to the EGFR inhibitor osimertinib and mutations in the KEAP1 pathway were associated with decreased time on tyrosine kinase inhibitor treatment in patients. Our study highlights how the impact of genetic alterations differ across oncogenic contexts and that the fitness landscape shifts upon treatment.
View details for DOI 10.1158/2159-8290.CD-20-1385
View details for PubMedID 33707235
- Genetic determinants of EGFR-driven lung cancer growth and therapeutic response in vivo AMER ASSOC CANCER RESEARCH. 2020
Complete, closed bacterial genomes from microbiomes using nanopore sequencing.
Microbial genomes can be assembled from short-read sequencing data, but the assembly contiguity of these metagenome-assembled genomes is constrained by repeat elements. Correct assignment of genomic positions of repeats is crucial for understanding the effect of genome structure on genome function. We applied nanopore sequencing and our workflow, named Lathe, which incorporates long-read assembly and short-read error correction, to assemble closed bacterial genomes from complex microbiomes. We validated our approach with a synthetic mixture of 12 bacterial species. Seven genomes were completely assembled into single contigs and three genomes were assembled into four or fewer contigs. Next, we used our methods to analyze metagenomics data from 13 human stool samples. We assembled 20 circular genomes, including genomes of Prevotella copri and a candidate Cibiobacter sp. Despite the decreased nucleotide accuracy compared with alternative sequencing and assembly approaches, our methods improved assembly contiguity, allowing for investigation of the role of repeat elements in microbial function and adaptation.
View details for DOI 10.1038/s41587-020-0422-6
View details for PubMedID 32042169
Improved high-molecular-weight DNA extraction, nanopore sequencing and metagenomic assembly from the human gut microbiome.
Short-read metagenomic sequencing and de novo genome assembly of the human gut microbiome can yield draft bacterial genomes without isolation and culture. However, bacterial genomes assembled from short-read sequencing are often fragmented. Furthermore, these metagenome-assembled genomes often exclude repeated genomic elements, such as mobile genetic elements, compromising our understanding of the contribution of these elements to important bacterial phenotypes. Although long-read sequencing has been applied successfully to the assembly of contiguous bacterial isolate genomes, extraction of DNA of sufficient molecular weight, purity and quantity for metagenomic sequencing from stool samples can be challenging. Here, we present a protocol for the extraction of microgram quantities of high-molecular-weight DNA from human stool samples that are suitable for downstream long-read sequencing applications. We also present Lathe ( www.github.com/bhattlab/lathe ), a computational workflow for long-read basecalling, assembly, consensus refinement with long reads or Illumina short reads and genome circularization. Altogether, this protocol can yield high-quality contiguous or circular bacterial genomes from a complex human gut sample in approximately 10 d, with 2 d of hands-on bench and computational effort.
View details for DOI 10.1038/s41596-020-00424-x
View details for PubMedID 33277629