MedGenome’s genomics solutions for precision medicine

ASHG 2023
Kushal Suryamohan, Ravi Gupta, Marco Corbo, Ramesh Menon, Megha Muraleedharan, Chaitanya E. Ramesh, Harsha Gowda, Hiranjith G.H., Vedam L. Ramprasad, Somasekar Seshagiri

MedGenome specializes in processing challenging samples including FFPE and low-quality input material. Our analysis includes comprehensive report with rich visualizations identifying all types of relevant DNA and RNA variants.

VaRTK – An accurate machine learning model trained on clinically curated variants to predict the variant pathogenicity score

ASHG 2023
Ravi Gupta, Manju Lakshmi, Charugulla Sai Yuva Sandeep, S. G. Thenral, Sandhya Nair, Anurag Gupta, Thiramsetti Sattibabu, Amit Parhar, Tamanna Golani, Sudarshana J. Pai, Tavleen Bajwa, Sakthivel Murugan S. M., Ramprasad V. L.

Identifying and prioritizing the disease causing variants from thousands of variants that are called during a whole genome and exome sequencing analysis is a time consuming and manual task. Pathogenicity based ranking of variants greatly improves the speed of report generation, in turn increasing the diagnostic yield.

MedGenome Inc. Broadens Single Cell Transcriptome and Epigenome Profiling: From Tissues to single nuclei RNA (snRNA) Sequencing and Data Analysis

Neha Verma, Kushal Suryamohan, Derek Vargas, Ekkirala Chaitanya Ramesh

Single-cell transcriptomics has revolutionized genomics and is now an integral part of therapeutics and diagnostics research. Single cell RNA sequencing (scRNA-seq) enables the analysis of gene expression at single cell resolution via droplet-based cell capture methods that rely on microfluidic instruments such as those developed by 10x genomics.

Multiple Platforms for Single Cell Genomics to Enable Biomarker Discovery in Immunotherapy

SLAS 2020
Ankita Das, Jing Wang, Kayla Lee, Derek Vargas, Gavin Washburn, Niyati Thosani, Vasumathi Kode, Nitin Mandloi, Angelica Lavallee, Amit Chaudhuri and Papia Chakraborty

Single cell genomic approaches can provide valuable insights into the complexity and heterogeneity of the cell types in the context of a tissue or tumor. However, challenges with the preparation of single cell suspensions, good cell viability and efficiently capturing diverse cell types in a mix via appropriate cell capture methods can override the utility of the approaches.

Applications of TCR repertoire analysis for biomarker discovery and beyond

World Pharma Week 2019
Ankita Das, Vasumathi Kode, Kayla Lee, Priyanka Shah, Xiaoshan "Shirley" Shi, Nitin Mandloi, Ravi Gupta, Amit Chaudhuri and Papia Chakraborty

T cell immunity provides significant therapeutic benefit to cancer patients treated with checkpoint inhibitors, however a very small fraction of patients typically respond to checkpoint inhibitors, and a smaller fraction of them have any long-term benefit. This can be attributed to the lack of prognostic and predictive biomarkers.

The value of studying the Indian population to identify novel genetic variants to inform mechanisms of disease and pharmacological response

ASHG 2018
A. Das, P. Raj, V. Gopalan, Hiranjith. G.H., E. Stawiski, S. Santhosh, R. Gupta, A. Chaudhuri, R. Gupta

While Genome wide association studies can shed light on the significance of variants in susceptibility to a disease or allow to stratify patients for specific therapeutic modalities, often variants that are rare and could be of significance are not identified in these studies.

The Ophthatome™ Knowledgebase : A curated knowledgebase of over 500,000 ocular disease phenotypic records coupled with analyses tools to enable novel discoveries for drug development and pharmacogenomics

ASHG 2018
A. Das, Nagasamy S, P. Raj, B. Muthu Narayanan, J. Somasekhar, T. Chandrasekhar, D. Kumar, A. Shetty, S. Das, S. Tejwani, P. Narendra, A. Ghosh

Medical big data analytics has applications in clinical decision, predictive/ prognostic modelling of disease progression, disease surveillance, public health and research.

OncoPeptTUME™ —A novel in-silico approach to model the tumor microenvironment and predict treatment efficacy and long-term survival benefits for immunotherapy applications

Next Gen Immuno-Oncology Congress
Xiaoshan “Shirley” Shi, Vasumathi Kode, Snigdha Majumder, Priyanka Shah, Ravi Gupta, Amit Chaudhuri, and Papia Chakraborty

Somatic mutations have been found to be a rich source of potential cancer vaccines (which have shown promise in treating late stage cancers) with minimal T cell tolerance. MedGenome has built a proprietary cancer vaccine prediction platform, OncoPeptVAC using a combination of features that include TCR binding, human leukocyte antigen (HLA) binding, gene expression and proteasomal processing.

A minigene platform to validate novel immunogenic peptides arising from somatic mutations as therapeutic cancer vaccines

AACR 2018

Papia Chakraborty3, Snigdha Majumder1, Rakshit Shah2, Jisha Elias1,2, Vasumathi Kode3, Yogesh Mistry2, Coral Karunakaran1, Priyanka Shah1, Malini Manoharan1, Bharti Mittal1, Sakthivel Murugan SM1, Lakshmi Mahadevan1, Ravi Gupta1, Amitabha Chaudhuri1,3 ** and Arati Khanna-Gupta1**

The MedGenome team has identified a germline mutation in an MMR pathway (the DNA mismatch repair pathway) gene – MLH1. Mutations in the MMR pathway genes have been known to be associated with Lynch syndrome wherein patients have a 70-80% lifetime risk of developing colorectal cancer (CRC).

A personalized cancer vaccine approach to treat Lynch syndrome

Molecular Med Tri_Con 2018
Priyanka, Malini, Kiran, Ravi, Rohit and Amit

Neoantigens, derived from somatic mutations are prime candidates for cancer vaccines. Currently, the available T-cell neoepitope prioritization pipelines rely primarily on two attributes – the class-I HLA-binding affinity of the mutant peptide compared to the wild-type counterpart, and the level of expression of the mutated gene in tumor cells.

A novel algorithm to identify TCR-binding somatic mutations from human cancers

AACR 2017

Ashwini Patil, MS1, Ravi Gupta, PhD1, Nitin Mandloi, MS1, Kiran V. Paul, MS1, Priyanka Shah, PhD1, Malini Manoharan, PhD1, Rohit Gupta, PhD1, and Amitabha Chaudhuri, PhD1

MedGenome conducted a study where TCGA data containing 9640 tumors from 33 different cancers was analyzed using its proprietary tumor microenvironment analysis platform OncoPeptTUMETM. It was observed that observed that CD8 T-cell content of tumors varies significantly from cancer to cancer, with a large proportion of tumors containing low CD8 T-cell infiltrate.

Tumor microenvironment analysis provides insights into the activity of CD8 T-cells and their impact on survival

Frontiers of Cancer Immunotherapy 2017
Ravi Gupta, Nitin Mandloi, Kiran Paul, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan and Amitabha Chaudhuri

MedGenome conducted a study in which TCGA data was analyzed to investigate the impact of CD8 T-cell infiltration on disease outcome. The analysis indicated that CD8 T-cell infiltration predicts favorable survival in certain cancers, whereas in other cancers it has no effect.

Integrated genomics approach of modeling tumors to assess their sensitivity to immune-mediated elimination

SITC Conference 2016
Nitin Mandloi, Ashwini Patil, Rekha Sathian, Aparna Mohan, Malini Manoharan, Ravi Gupta and Amit Chaudhuri

With the knowledge that tumors lacking CD8 T cells are less responsive to checkpoint control blockade, MedGenome’s scientists have chosen to study a set of core pathways associated with the absence or presence of specific immune cell types in tumors, which can be modulated to alter the immune profile of these unresponsive tumors and sensitize them to checkpoint control blockade.

Differential gene expression and tumormutanome analysis reveal significantly enriched pathways associated with higher tumor burden of M1 and M2 macrophages

Tumor Immunology and Immunotherapy 2016
Ravi Gupta, Nitin Mandloi, Ashwini Patil, Malini Manoharan, Rekha Sathian, Kiran Paul and Amitabha Chaudhuri

In the backdrop of the remarkable success checkpoint control inhibitors have shown in treating a variety of different cancers, this study focused on deeper assessment of the tumor and its microenvironment at the genetic and phenotypic level. Data from recent clinical trials have unequivocally established that the tumor microenvironment significantly impacts the efficacy of immune-oncology drugs.

Analysis of tumor microenvironment identifies pathways predicting response to checkpoint control inhibitors: A case study comparing the immune microenvironment of uveal melanoma vs skin cutaneous melanoma

CIMT-AACR Cancer Immunotherapy Conference 2016
Ashwini Patil, Nitin Mandloi, Rekha Sathian, Aparna Mohan, Malini Manoharan, Ravi Gupta and Amit Chaudhuri

With only a few studies having analyzed the interaction between granulocytic and monocytic myeloid derived suppressor cells in human cancers, MedGenome’s scientists have chosen to investigate their immune suppressive effect on the tumor microenvironment in this study.

OncoPeptTUME™ identifies tumor intrinsic and extrinsic factors promoting infiltration of granulocytic myeloid derived suppressor cells (G-MDSCs) in human cancers

Ravi Gupta, Kiran Paul, Nitin Mandloi, Malini Manoharan and Amit Chaudhuri

A critical phase in the development of cancer is the conversion of growth-suppressive normal tissue microenvironment into a growth-promoting tumor microenvironment. MedGenome conducted a study to interrogate the tumor epithelial and the stromal compartments in a cohort of tongue and buccal cancers, using NGS sequencing.

Differential gene expression profile of tongue and buccal cancers produce unique and shared vaccine candidates for cancer immunotherapy

ASCO Annual Meeting 2016
PapManoharan Malini, Iyer Laxman, Priyanka Shah, Kiran Paul, Amit Choudhary, Ravi Gupta

Large scale sequencing of cancer genomes have revealed several mutations that remain uncharacterized, of which only few mutations are tested for activating or loss of function. MedGenome conducted a study which utilized in-silico method to characterize 4096 mutations in 190 cancer census genes spread across 33 cancer groups.

A Structural Approach to Identify Activating and Loss of Function Somatic Mutation

Big Data Bioinformatics Conference 2016
R. Gupta, N. Mandloi, M. Manoharan, Kiran V. Paul, Deborah Consiglio and Amit Chaudhuri

It is known that tumor cells employ a variety of immune-evasive mechanisms. Of particular interest is the tumor-intrinsic mechanisms that prevent T-cells from infiltrating into the tumor microenvironment.

OncoPeptTUME™ identifies pathways enriched in T-cell inflamed tumors

Biomarker Congress 2016
K. Kumaramangalam, S. Sharan, R. Nathan, D. Consiglio, G.H. Hiranjith, R. Gupta and A. Chaudhuri

At the conference, MedGenome introduced OncoPept- its integrated platform that combines powerful analytics to analyze exome and RNA-seq data to quantitate the epithelial, stromal and immune cell infiltration, thereby producing a holistic view of the tumor and the tumor microenvironment.

OncoPept is an end-to-end genomic solution to discover novel therapeutics and biomarkers in the cancer immunotherapy space

PEGS Cancer Immunotherapy Conference Poster 2016

Viswanathan S.1, Gupta R.1, Khanna-Gupta A.1, Chaudhuri A.2

The study titled “Whole Genome Sequencing data from the Wellderley study identifies rare variants in genes associated with diabetes and cardiomyopathy” involved the analysis of publicly available whole genome sequence data (WGS) of 454 healthy elderly Caucasian individuals from the Wellderly study.

Differential gene expression profile of tongue and buccal cancers produce unique and shared vaccine candidates for cancer immunotherapy

Novel Immunotherapeutics Conference 2016
R. Gupta, K. V. Paul, Nitin Mandloi V. Ramprasad, R. Vijayalakshmi,* A. Gupta and Amitabha Chaudhuri

Head and Neck squamous cell carcinoma (HNSCC) comprises of tumors arising from multiple sites of the upper aerodigestive tract. Cancers of buccal and tongue are highly prevalent worldwide and account for significant morbidity and mortality.

OncoPept™: A platform to interrogate tumors in search of novel cancer immunotherapy targets and biomarkers

Next Generation Sequencing Conference 2016
R. Gupta, K. V. Paul, V. Ramprasad, R. Vijayalakshmi, A. Gupta and Amitabha Chaudhuri

MedGenome presented results from a study that examined differential gene expression, that identified unique and shared vaccine candidates that can be used in combination therapies. The study involved analysis of published genomics data from over 400 buccal and tongue cancer samples to identify potential vaccine candidates using MedGenome’s proprietary analysis platform.

Whole Genome Sequencing data from the Wellderley study identifies rare variants in genes associated with diabetes and cardiomyopathy

Diabetes Summit 2016
Ravi Gupta, Kiran Paul, Nitin Mandloi, Malini Manoharan, Kartik Kumaramangalam, Sam Santhosh and Amitabha Chaudhuri

OncoMD Cancer Analytics Platform combines tumor mutation profiles, expression signatures, copy number variations, epigenetic alterations and drug sensitivity to create a holistic view of human cancer enabling discovery of new targets for therapy and prognosis.

Molecular epidemiological analysis of oral cancer in the Indian population reveals region-specific differences in the spectrum of driver mutations and oncogenic pathways

AACR-JCA Conference 2016
R. Gupta, K. V. Paul, N. Mandloi, K. Kumaramangalam, D. Consiglio and A. Chaudhuri

OncoPeptTM is an integrated platform that combines powerful analytics to analyze exome and RNA-seq data with multistep prioritization to select cancer vaccine candidates as therapeutics. The platform generates neo-antigens from different types of genetic alterations such as SNVs, indels and fusion genes to generate a library of peptides that are automatically interrogated through the multiple prioritization steps.

OncoMD: A powerful genomics data analysis and interpretation platform for cancer discovery research

AACR Annual Meeting 2016
Ravi Gupta, Kiran V. Paul, Vedam Ramprasad, Arati Gupta, Debbie Consiglio1 and Amitabha Chaudhuri

This study reveals the functionality of OncoPept, MedGenome’s proprietary cancer immunotherapy platform, that predicts T-cell neo-epitopes from human and mouse cancers. Multiple pre-clinical and clinical studies have demonstrated the importance of the characterization of T-cell neo epitopes and its role in the development of cancer vaccines.

OncoPeptTM interrogates the mutational landscape of tongue and buccal cancer in search of novel cancer immunotherapy targets and biomarkers

AACR 2018
R. Gupta, V. Ramprasad, K. Kumaramangalam, A. Gupta, S. Santhosh and A. Chaudhuri

The poster depicts an oral cancer study to examine the molecular basis of region-specific differences by profiling four distinct oral cancer cohorts collected from the Northern, Eastern, Southern and Western regions of India. The cohorts in the study were such that it maximized the probability that all individuals shared similar environmental and lifestyle factors within a given region.

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