Ashok K Sharma, PhD Computational Biology

Current Role:

📚 Scientist-II, Computational Biology, Takeda, San Diego

  • As part of the Computational Biology and Toxicology (CBT) team at the Global Drug Safety Research Evaluation (DSRE), I drive safety risk assessment through predictive modeling and large-scale transcriptomic data analysis, enhancing drug discovery research efficiency and consistency.
  • Developing AI/ML models for predicting toxicological endpoints like Hepatotoxicity (DILI) and Neurotoxicity, and supporting the Oligo working group with off-target identification strategies to improve the safety and effectiveness of different modalities, including small molecules and biologics.

Previous Experience:

📚 Postdoctoral Researcher, Cedars Sinai Medical Center

  • Thoroughly analyzed and integrated multi-omics datasets, aiming to identifying pathogenic factors in Inflammatory Bowel Disease (IBD). Projects included:
    • Analyzed Imaging Mass Cytometry Datasets for Bacterial Co-Localization in Crohn's Disease.
    • Quantified bacterial growth rates from metagenomic datasets to identify activities associated with Crohn’s disease progression.
    • Investigated microbial role in SARS-COV-2 persistence in the GI Tract.
    • Explored the impact of Human Milk Oligosaccharides on Gene Expression and Immune Response in the Intestines.

📚 Postdoctoral Associate, University of Minnesota Twin Cities

  • Delved into understanding microbiome-host interactions in both animal and human models under diverse physiological conditions. Projects included:
    • Primates Gut Bacteriome & Mycobiome defies evolutionary constraints.
    • Gut microbial functional adaptations influenced by diet and lifestyle factors.
    • Oral microbiome studies in HNSCC and ex-vivo dental caries.
    • Animal microbiome research on Beef cattle, Horses and other domestic animals.

Education:

  • Ph.D. in Computational Biology, IISER Bhopal
    • I applied computational biology to various domains such as drug discovery and microbiome-host interactions, laying the foundation for my passion in computational biology and its applications in addressing key questions from complex biological datasets.

CV / Linkedin / Email / Google Scholar / Twitter / Github

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Research

I was deeply engaged in the development and application of AI/machine learning and other data-driven methodologies to discern the impact of the microbiome on the general growth, health, and well-being of both animals and humans. A significant portion of my research focused on deducing diet-microbiome-host interactions from multi-omics libraries. The following is a list of my representative papers from that time:

PontTuset The role of the intestine in metabolic dysregulation in murine Wilson disease
Gaurav V Sarode, Tagreed Mazi, Kari Neier, Shibata, Noreene M, Guillaume Jospin , Nathaniel Harder H.O, AmandaCaceres, Marie Heffern , Ashok K. Sharma, Shyam More, Maneesh Dave, Shannon Schroeder, Li Wang, Janine LaSalle, Svetlana Lutsenko, Valentina Medici
Hepatology Communications, 2023
paper

Intestine-specific ATP7B deficiency affected both intestinal and systemic response to a high-fat challenge but not the microbiome profile, at least at early stages.

PontTuset Functional signatures of ex-vivo dental caries onset
Dina Moussa, Ashok K. Sharma, Tamer Mansour, Bruce Witthuhn, Jorge Perdigao Henriques, Joel Rudney, Conrado Aparicio Badenas, Andres Gomez
Journal of Oral Microbiology, 2022
raw data / paper

We optimize ex-vivo model integrated with the advanced imaging combined with multi-omics libraries to detect functional signatures associated with dental caries.

PontTuset In-Patient Antibiotic Exposure Promotes SARS-COV-2 Persistence in the Gi Tract in Covid-19 Admitted Patients
Ashok K. Sharma, Anthony Martin, Jacob Moskowitz, Stephanie Bora, Katherine Lagree, Pieter Dorrestein, David Underhill, Rob Knight, Peter Chen, Suzanne Devkota
Gastroenterology, 2022   (Oral Presentation)
raw data / presentation / abstract

The heavy-dose antibiotic regimen administered to COVID-19 in-patients is associated with viral persistence of SARS-COV-2 in the GI tract, suggesting an important role of the gut microbiome in excluding SARS-COV-2 from the GI tract, perhaps by competitive exclusion or promoting interferon responses.

PontTuset Human Milk Oligosaccharides Impact Cellular and Inflammatory Gene Expression and Immune Response
Fernanda Rosa, Ashok K. Sharma, Manoj Gurung, David Casero, Katelin Matazel, Lars Bode, Christy Simecka, Ahmed Elolimy, Patricia Tripp, Christopher E Randolph, Timothy W Hand, D Keith Williams, Tanya LeRoith, Laxmi Yeruva
Frontiers in Microbiology , 2022
raw data / paper / project page

In this study, we have shown that HMO administration appears to promote immunoregulatory effects at the gene expression level in the absence of gut microbiota.

PontTuset Dietary zinc restriction affects the expression of genes related to immunity and stress response in the small intestine of pigs
Ramya Lekha Medida, Ashok K. Sharma, Yue Guo, Lee Johnston, Pedro Urriola, Andres Gomez, Milena Saqui Salces
Journal of Nutritional Science, 2022
raw data / paper

The main goal of the present study was to understand intestinal responses to nutritional Zn restriction and supplementation that could influence overall health of the animal and indicate early changes in response to Zn restriction.

PontTuset Human Assessing the Effect of Smokeless Tobacco Consumption on Oral Microbiome in Healthy and Oral Cancer Patients
Rituja Saxena, Vishnu Prasoodanan, Sonia Vidushi Gupta, Sudheer Gupta, Prashant Waiker, Atul Samaiya, Ashok K. Sharma, Vineet K. Sharma
Frontiers in Cellular and Infection Microbiology , 2022
raw data / paper

In this study, we profiled oral microbiome of healthy and oral cancer patients to decipher the microbial dysbiosis due to the consumption of smokeless-tobacco-based products and also revealed the tobacco-associated microbiome.

PontTuset Microbiome network traits in the rumen predict average daily gain in beef cattle under different backgrounding systems
Bobwealth Oakina Omontese, Ashok K. Sharma, Samuel Davison, Emily Jacobson, Alfredo DiCostanzo, Megan Webb, Andres Gomez
Animal Microbiome , 2022
raw data / paper

This longitudinal study was designed to assess how BKG affects rumen bacterial communities and average daily gain (ADG) in beef cattle.

PontTuset The primate gut mycobiome-bacteriome interface is impacted by environmental and subsistence factors
Ashok K. Sharma, Samuel Davison, Barbora Pafco, Jonathan B. Clayton, Jessica Rothman, Matthew McLennan, Marie Cibot, Terence Fuh, Roman Vodicka, Carolyn Jost Robinson, Klara Petrzelkova, Andres Gomez
npj Biofilms and Microbiomes , 2022
raw data / paper / project page

Our main findings indicate a strong influence of host-ecological factors including diet and lifestyle in shaping the fungal community composition in the primate’s gut. This is in contrast with the gut bacterial fraction, which seems to be more influenced by the host genetics.

PontTuset Western and non-western gut microbiomes reveal new roles of Prevotella in carbohydrate metabolism and mouth–gut axis
Vishnu Prasoodanan, Ashok K. Sharma, Shruti Mahajan, Darshan Dhakan, Joy Scaria, Vineet K. Sharma

npj biofilms and microbiomes , 2021
raw data / paper

A population-wide analysis was carried out on 586 healthy samples from western and non-western populations including the largest Indian cohort comprising of 200 samples, and 189 Inflammatory Bowel Disease samples from western populations.

PontTuset Traditional Human Populations and Nonhuman Primates Show Parallel Gut Microbiome Adaptations to Analogous Ecological Conditions
Ashok K. Sharma, Klara Petrzelkova, Barbora Pafco, Carolyn Jost Robinson, Terence Fuh, Brenda Anne Wilson, Rebecca M. Stumpf, Manolito Torralba, Ran Blekhman, Bryan White, Karen E. Nelson, Steven Leigh, Andres Gomez

mSystems , 2020
raw data / paper / project page

The results of this study highlight parallel gut microbiome traits in human and nonhuman primates, depending on subsistence strategy.

PontTuset The Horse Gut Microbiome Responds in a Highly Individualized Manner to Forage Lignification
Andres Gomez, Ashok K. Sharma, Amanda Grev, Craig C Sheaffer, Krishona Martison

Journal of Equine Veterinary Science , 2020
raw data / paper

Results in this study indicate that the horse gut microbiome responds in an individualized manner to changes in the amount of acid detergent lignin in alfalfa hay, potentially impacting several feed digestibility characteristics.

PontTuset Molib: A machine learning based classification tool for the prediction of biofilm inhibitory molecules
Gopal Narayan Srivastava, Aditya Malwe, Ashok K. Sharma, Vibhuti Shastri, Keshav Hibare, Vineet K. Sharma

Genomics , 2020
paper / web page

We developed the ‘Molib’ tool to predict the biofilm inhibitory activity of small molecules.

PontTuset Oral Microbiome Profiling in Smokers with and without Head and Neck Cancer Reveals Variations Between Health and Disease
Ashok K. Sharma, William Debusk, Irina Stepanov, Andres Gomez, Samir Khariwala

Cancer Prevention Research , 2020
raw data / paper / project page

To determine microbial associations with oral/head and neck cancer (HNSCC) among tobacco users, we characterized oral microbiome composition in smokers with and without HNSCC. 16S rRNA MiSeq sequencing was used to examine the oral mucosa microbiome of 27 smokers with (cases) and 24 without HNSCC (controls).

PontTuset Association of Flavonifractor plautii, a Flavonoid-Degrading Bacterium, with the Gut Microbiome of Colorectal Cancer Patients in India
Ankit Gupta, Darshan Dhakan, Abhijit Maji, Rituja Saxena, Vishnu Prasoodanan, Shruti Mahajan, Joby Pulikkan, Kurian Jacob, Andres Gomez, Joy Scaria, Katherine R. Amato, Ashok K. Sharma, Vineet K. Sharma

mSystems , 2019
raw data / paper

This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC.

PontTuset Plasticity in the Human Gut Microbiome Defies Evolutionary Constraints
Andres Gomez, Ashok K. Sharma**, Elizabeth K Mallott, Klara Petrzelkova, Carolyn Jost Robinson, Carl J Yeoman, Franck Carbonero, Barbora Pafco, Jessica Rothman, Alexander Ulanov, Klara Vlckova, Katherine R. Amato, Stephanie L. Schnorr, Nathaniel J Dominy, David Modry, Angelique Todd, Manolito Torralba, Karen E. Nelson, Michael Burns, Ran Blekhman, Melissa J. Remis, Rebecca M. Stumpf, Brenda Anne Wilson, Rex Gaskins, Paul A Garber, Bryan White, Steven Leigh

mSphere , 2019
paper / project page

The results of this study indicate a discordance between gut microbiome composition and evolutionary history in primates, calling into question previous notions about host genetic control of the primate gut microbiome.

PontTuset Mapping gastrointestinal gene expression patterns in wild primates and humans via fecal RNA-seq
Ashok K. Sharma, Barbora Pafco, Klara Vlckova, Barbora Cervena Jakub Kreisinger, Samuel Davison, Karen Beeri, Terence Fuh, Steven Leigh, Michael Burns, Ran Blekhman, Klara Petrzelkova, Andres Gomez

BMC Genomics , 2019
raw data / paper

Results in this study suggest that fecal RNA-seq, targeting gastrointestinal epithelial cells can be used to evaluate primate intestinal physiology and gut gene regulation, in samples obtained in challenging conditions in situ.

PontTuset Gut microbiome composition of wild western lowland gorillas is associated with individual age and sex factors
Barbora Pafco, Ashok K. Sharma** Klara Petrzelkova, Klara Vlckova, Angelique Todd, Carl J Yeoman, Brenda Anne Wilson, Rebecca M. Stumpf, Bryan White, Karen E. Nelson, Steven Leigh, Andres Gomez

American Journal of Biological Anthropology , 2019
paper

Objective of this study was to determine the associations between an individual's age and sex on the diversity and composition of the gut microbiome in wild western lowland gorillas.

PontTuset The unique composition of Indian gut microbiome, gene catalogue, and associated fecal metabolome deciphered using multi-omics approaches
Darshan Dhakan, Abhijit Maji, Ashok K. Sharma, Rituja Saxena, Joby Pulikkan, Tony Grace, Andres Gomez, Joy Scaria, Katherine R. Amato, Vineet K. Sharma

GigaScience , 2019
raw data / raw data

We analyzed the gut microbiome of 110 healthy individuals from two distinct locations (North-Central and Southern) in India using multi-omics approaches, including 16S rRNA gene amplicon sequencing, whole-genome shotgun metagenomic sequencing, and metabolomic profiling of fecal and serum samples.

PontTuset Genome Sequence of Peacock Reveals the Peculiar Case of a Glittering Bird
Subham K. Jaiswal, Ankit Gupta, Rituja Saxena, Vishnu Prasoodanan, Ashok K. Sharma, Parul Mittal, Ankita Roy, , Nagarjun Vijay, Vineet K. Sharma

Frontiers in Genetics , 2018
raw data / paper

Here, we report the first genome sequence and comparative analysis of peacock with the high quality genomes of chicken, turkey, duck, flycatcher and zebra finch.

PontTuset Mechanistic and structural insight into promiscuity based metabolism of cardiac drug digoxin by gut microbial enzyme
Kundan Kumar, Subham K. Jaiswal, Gaurao Dhoke, Gopal Narayan Srivastava, Ashok K. Sharma, Vineet K. Sharma

Journal of Cellular Biochemistry , 2017
paper

We report the atomistic details and energy economics binding and metabolism of Digoxin by the Cgr2 protein of Eggerthella lenta DSM 2243.

PontTuset Prediction of anti-inflammatory proteins/peptides: an insilico approach
Sudheer Gupta, Ashok K. Sharma**, Vibhuti Shastri, Midhun K. Madhu Dhakan, Vineet K. Sharma

Journal of Translational Medicine , 2017
paper / web page

In this study, we have developed a prediction tool for the classification of peptides as anti-inflammatory epitopes or non anti-inflammatory epitopes.

PontTuset Approach for the prediction of species-specific biotransformation of xenobiotic/drug molecules by the human gut microbiota
Ashok K. Sharma, Subham K. Jaiswal Nikhil Chaudhary, Vineet K. Sharma

Scientific Reports , 2017
paper / web page

DrugBug is a computational approach to predict the metabolic enzymes and gut bacterial species, which can potentially carry out the biotransformation of a xenobiotic/drug molecule

PontTuset ToxiM: A Toxicity Prediction Tool for Small Molecules Developed Using Machine Learning and Chemoinformatics Approaches
Ashok K. Sharma, Gopal Narayan Srivastava, Ankita Roy, Vineet K. Sharma

Frontiers in Pharmacology , 2017
paper / web page

ToxiM is a machine-learning based binary classifier for the prediction of toxicity of molecules. Regression models for CaCo-2 permeability and Aqueous solubility has been provided to support the predicted toxicity for a given molecule. For the batch processing please download standalone version of ToxiM from Dataset page.

PontTuset Prediction of Biofilm Inhibiting Peptides: An In silico Approach
Sudheer Gupta, Ashok K. Sharma, Subham K. Jaiswal, Vineet K. Sharma

Frontiers in Microbiology , 2016
paper / web page

BioFin is a unique computational method for the prediction of biofilm inhibiting peptides. The experimentally validated biofilm inhibiting peptides sequences and their features were used for the training.

PontTuset ProInflam: a webserver for the prediction of proinflammatory antigenicity of peptides and proteins
Sudheer Gupta, Midhun K. Madhu Dhakan, Ashok K. Sharma, Vineet K. Sharma

Journal of Translational Medicine , 2016
paper / web page

ProInFlam is a unique tool for the computational identification of proinflammatory peptide antigen/candidates and provides leads for experimental validations

PontTuset Prediction of peptidoglycan hydrolases- a new class of antibacterial proteins
Ashok K. Sharma, Sanjiv Kumar, Harish K., Darshan Dhakan, Vineet K. Sharma

BMC Genomics , 2016
paper / web page

The present tool helps in the identification and classification of novel peptidoglycan hydrolases from complete genomic or metagenomic ORFs. To our knowledge, this is the only tool available for the prediction of peptidoglycan hydrolases from genomic and metagenomic data.

PontTuset Reconstruction of Bacterial and Viral Genomes from Multiple Metagenomes
Ankit Gupta, Sanjiv Kumar, Vishnu Prasoodanan, Harish K., Ashok K. Sharma, Vineet K. Sharma

Frontiers in Microbiology , 2016
paper

In this work, Binning-Assembly approach has been proposed and demonstrated for the reconstruction of bacterial and viral genomes from 72 human gut metagenomic datasets.

PontTuset Woods: A fast and accurate functional annotator and classifier of genomic and metagenomic sequences
Ashok K. Sharma, Ankit Gupta, Sanjiv Kumar, Darshan Dhakan, Vineet K. Sharma

Genomics , 2015
paper / web page

Integrated approach for fast and accurate functional annotation of proteins in both genomic and metagenomic datasets. It is available as stand-alone tool as well as a publicly available web-server.

PontTuset The 16S Classifier: A Tool for Fast and Accurate Taxonomic Classification of 16S rRNA Hypervariable Regions in Metagenomic Datasets
Nikhil Chaudhary, Ashok K. Sharma**, Piyush Agarwal, Ankit Gupta, Vineet K. Sharma

PLOS ONE , 2015
paper / web page

'16S Classifier' is a Random Forest based tool which is developed to carry out fast, efficient and accurate taxonomic classification of 16S rRNA sequences. It has the unique ability to classify small Hypervariable Regions of 16S rRNA.


Source code credit to Dr. Jon Barron