Gregory D. Sepich‐Poore

ORCID: 0000-0002-3443-3715
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About
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Research Areas
  • Gut microbiota and health
  • Cancer Genomics and Diagnostics
  • Genomics and Phylogenetic Studies
  • Epigenetics and DNA Methylation
  • Cancer Research and Treatments
  • Molecular Biology Techniques and Applications
  • Cancer Cells and Metastasis
  • Microbial Community Ecology and Physiology
  • Bacteriophages and microbial interactions
  • Radiomics and Machine Learning in Medical Imaging
  • Tryptophan and brain disorders
  • Metabolomics and Mass Spectrometry Studies
  • Bacterial Identification and Susceptibility Testing
  • Cell Image Analysis Techniques
  • Cancer-related molecular mechanisms research
  • Cancer Immunotherapy and Biomarkers
  • Lung Cancer Diagnosis and Treatment
  • Immunotherapy and Immune Responses
  • Systemic Lupus Erythematosus Research
  • Single-cell and spatial transcriptomics
  • Fungal Biology and Applications
  • Prostate Cancer Diagnosis and Treatment
  • Advanced Biosensing Techniques and Applications
  • Urinary Tract Infections Management
  • Enterobacteriaceae and Cronobacter Research

La Jolla Bioengineering Institute
2021-2025

University of California, San Diego
2020-2025

Northwestern University
2024

Midwestern University
2024

Micron (United States)
2022-2023

Cancer-microbe associations have been explored for centuries, but cancer-associated fungi rarely examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 types in four independent cohorts. We report fungal DNA cells at low abundances many major human cancers, with differences community compositions that differ among types, even when accounting technical background. Fungal histological staining of tissue microarrays...

10.1016/j.cell.2022.09.005 article EN cc-by Cell 2022-09-01

We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as minimum for assessing diversity of microbial communities and their relevance environmental factors. This approach is independent taxonomic classification, granting possibility maximal resolution community composition, organizes features into an accurate hierarchy using phylogenomic tree. The outputs are suitable contemporary...

10.1128/msystems.00167-22 article EN mSystems 2022-04-04

Periodontal disease is more common in individuals with rheumatoid arthritis (RA) who have detectable anti-citrullinated protein antibodies (ACPAs), implicating oral mucosal inflammation RA pathogenesis. Here, we performed paired analysis of human and bacterial transcriptomics longitudinal blood samples from patients. We found that patients periodontal experienced repeated bacteremias associated transcriptional signatures ISG15 + HLADR hi CD48 high S100A2 pos monocytes, recently identified...

10.1126/scitranslmed.abq8476 article EN Science Translational Medicine 2023-02-22

Abstract In 2020, we identified cancer-specific microbial signals in The Cancer Genome Atlas (TCGA) [1]. Multiple peer-reviewed papers independently verified or extended our findings [2–12]. Given this impact, carefully considered concerns by Gihawi et al. [13] that batch correction and database contamination with host sequences artificially created the appearance of cancer type-specific microbiomes. (1) We tested comparing raw Voom-SNM-corrected data per-batch, finding predictive...

10.1038/s41388-024-02974-w article EN cc-by Oncogene 2024-02-23

Abstract The pursuit of highly sensitive and specific cancer diagnostics based on cell‐free nucleic acids isolated from minimally invasive liquid biopsies has been an area intense research commercial effort for at least two decades. Most these tests detect cancer‐specific mutations or epigenetic modifications circulating DNA derived tumor cells (ctDNA). Although recent FDA approvals both single multianalyte biopsy companion diagnostic assays are proof the tremendous progress made in this...

10.1002/viw.20200118 article EN cc-by View 2022-01-01

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, methodological framework. Without such framework, oncology will collect piecemeal results, with scant dialogue between the scientific communities studying cancer. We argue one important way forward in...

10.1111/brv.12971 article EN cc-by-nc-nd Biological reviews/Biological reviews of the Cambridge Philosophical Society 2023-05-08

Abstract As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient filtration using prior human references can introduce false sex biases and inadvertently permit flow-through of host-specific during bioinformatic analyses, which could be exploited individual identification. To address these issues, we benchmark three methods varying throughput,...

10.1038/s41467-025-56077-5 article EN cc-by Nature Communications 2025-01-18

Abstract The cancer microbiome field tremendously accelerated following the release of our manuscript nearly three years ago 1 , including direct validation type-specific conclusions in independent, international cohorts 2,3 and tumor microbiome’s adoption into hallmarks 4 . Disentangling contamination signals from biological is an important consideration for this research field. Therefore, despite numerous, high-impact, peer-reviewed papers that either validated or extended them using data...

10.1101/2023.02.10.528049 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2023-02-13

Abstract We introduce Operational Genomic Unit (OGU), a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing diversity of microbial communities and their relevance environmental factors. This approach is independent from taxonomic classification, granting possibility maximal resolution community composition, organizes features into an accurate hierarchy using phylogenomic tree. The outputs are suitable...

10.1101/2021.04.04.438427 preprint EN cc-by-nc-nd bioRxiv (Cold Spring Harbor Laboratory) 2021-04-06

Quantifying the differential abundance (DA) of specific taxa among experimental groups in microbiome studies is challenging due to data characteristics (e.g., compositionality, sparsity) and study designs repeated measures, meta-analysis, cross-over). Here we present BIRDMAn (

10.1101/2023.01.30.526328 preprint EN cc-by-nc bioRxiv (Cold Spring Harbor Laboratory) 2023-02-02

Inter-individual differences in the gut microbiome are linked to alterations inflammation and blood–brain barrier permeability, which may increase risk of depression people with HIV (PWH). The profile blood, is considered by many be typically sterile, remains largely unexplored. We aimed characterize blood plasma composition assess its association major depressive disorder (MDD) PWH without (PWoH). In this cross-sectional, observational cohort, we used shallow-shotgun metagenomic sequencing...

10.3390/microorganisms11041022 article EN cc-by Microorganisms 2023-04-14

Abstract Sensitive removal of host genetic information (i.e., depletion) is a key first step towards accurate classification potential microbial DNA sequences in low-biomass samples, such as human tumors. Inadequate filtration reads prior to can cause false positives, biasing biological conclusions. Previous computational depletion pipelines predominantly employed the reference genome GRCh38 (hg38), which lacks diversity population and excludes substantial portions Y-chromosome. To address...

10.1158/1538-7445.am2024-4954 article EN Cancer Research 2024-03-22

<title>Abstract</title> As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient filtration using prior human references can introduce false sex biases and inadvertently permit flow-through of host-specific during bioinformatic analyses, which could be exploited individual identification. To address these issues, we benchmark three methods...

10.21203/rs.3.rs-4721159/v1 preprint EN cc-by Research Square (Research Square) 2024-10-23

Abstract While the study of tumor microbiome and its effects on cancer biology has expanded considerably over last few years, most this research focused bacteria viruses, leaving behind fungal kingdom. Recently, a studies have demonstrated that specific fungi may promote progression, stressing importance comprehensively studying mycobiome effects. To address this, we characterized in 1,183 human tumors their adjacent tissues, originating from eight major solid types. Staining imaging...

10.1158/1538-7445.am2022-3054 article EN Cancer Research 2022-06-15

Abstract Introduction: Links between cancer and microbes date back four millennia (Sepich-Poore et al. 2021. Science). Recently, we found that microbial DNA is detectable in tumor tissues patient blood from many human types (Poore 2020. Nature). These intratumoral bloodborne microbiomes were distinct types, normal malignant tissues, present cell-free plasma samples. However, the practical utility of (cf-mbDNA) as a bona fide liquid biopsy diagnostic, including its applicability early-stage...

10.1158/1538-7445.am2023-5713 article EN Cancer Research 2023-04-04
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