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iOMICS Clinical & OmniaOmics based (CDx)-drug-(Rx) solution
Asoke K Talukder, PhD & Mohamood AdhilInterpretOmics
iOMICS Clinical: OverviewiOMICS Clinical & Omnia is a (CDx)-drug-(Rx) software solution for Biomarker and Drug target discovery. It helps Pharmaceutical companies and Hospitals to associate targeted drugs/companion diagnostic pairs seamlessly
iOMICS Clinical (Big Data Analytics for Biomarker discovery):• Discovery: Phenotype Modeling, Drug Target Identification and Validation • Pre-Clinical: Toxicogenomics • Clinical Trial: Trial Stratification and Companion Diagnostics (CDx)
Omnia (Knowledge Base):• Disease centric Multi-omics knowledge base• Integration and Functional annotation for identification of significant Biomarkers
© Interpretomics www.interpretomics.co
Currently 42% of all drugs and 73% of oncology drugs in development are targeted drugs. This market is worth approximately $42 billion and should be worth over $60 billion by 2019.
(The Journal of Precision Medicine Vol1 Issue 2 Page no 31)
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iOMICS Clinical
© Interpretomics www.interpretomics.co 3
Uses Top-down and Bottom-up approach for Biomarker identification
In Top-down, user generated High-throughput data is used to scale down the molecular information based on Statistical characteristics
In Bottom-up, reference Biological databases and in-house database (Omnia) are used to annotate, analyse and integrate
Finally, Integrative approach is used to identify significant biomarkers using results from Top-down and Bottom-up approach
iOMICS Clinical: Systems Biology Approach
© Interpretomics www.interpretomics.co 4
iOMICS Clinical: Target Identification - 3 Step Process
Experimental Data Analysis (Case/Control):
> Gene Expression > Metabolomics
> Proteomics
Can also use experimental results stored in Omnia
Integrative Analysis
> Metabolic Pathways > Signaling Pathways > Protein interaction
Networks
Flux balance analysis Metabolic flux comparison Expression level changes
Network neighborhood analysis Key pathway identification Central pathway genes
Protein Functional Analysis In-silico knockout Validation based scoring using properties such as:
Protein class Localization Frequency Network centrality
Data
Analysis
Validation
> Omnia (Knowledge base) > Literature Mining
© Interpretomics www.interpretomics.co 5
iOMICS Clinical: Lung Cancer Case StudyData: Lung Squamous Cell Carcinoma (PMID: 25189482)
Data Analysis and Network Based Target Identification
Target Assessment Protein class Protein localization Protein structure Contribution in interaction network Protein-disease association
Statistics in Omnia Frequency of gene-disease association Functional association of gene with disease Population-wide statistics of variations in
the gene and mutation prioritization Molecular signature based clustering for
target population identification Existing drugs for the molecule
Based on networks including the protein interaction network, cellular signaling network and human metabolic network
Networks are calibrated according to the cell types
Network properties are studied to obtain the genes
© Interpretomics www.interpretomics.co 6
iOMICS Clinical: Patient Stratification
Clinical Variation Gene/Protein Expression
• Clinical marker identification for phenotype classification (example: responders and non-responders)
• Grouping clinical variables into Demographics, Environmental, and Phenotypes
• Supports all types of variables such as Continous, Categorical, Discrete, and Binary
• Statistical tools used for modeling are Linear regression, Logistic regression, Cox regression, and Decision tree
• Molecular marker (Mutation) identification for Phenotype classification (example: responders and non-responders)
• Supports raw (FASTQ), BAM, and VCF files for DNA data
• Integrates Clinical with Variation data for Biomarker identification, Functional analysis, and Annotation with Omnia
• Statistical tools used for Modeling are Cox regression and Binomial-naive Bayes classifier
Molecular marker (Gene Expression) Identification for group classification (example: responders and non-responders)
Supports raw (FASTQ and CEL), BAM, and CSV for RNA data
Integrates Clinical with Gene expression data for Biomarker identification, Functional analysis, and Annotation with Omnia
Statistical tools used for Modeling are Cox regression and LASSO
© Interpretomics www.interpretomics.co 7
iOMICS Clinical: Patient Stratification - Illustration
Sample Labeling
Feature Selection
Model Selection
Data: Lung Squamous Cell Carcinoma (PMID: 25189482)
Three significant clinical features ('TNM', 'Chemotherapy-Neoadjuvant therapy', 'Tobacco-Smoking') separating two groups (responders and non-responders)
Data: Lung Squamous Cell Carcinoma (PMID: 25189482)
Bio-markers for drug response: 10 genes (RNFT2, RHPN2, PROX1, CNTN1, FGFBP1, TINCR, OLFML2A, CYP26B1, SALL3, AREG)
Responders Group
Non-Responders Group
Data: Uveal Melanoma (PMID: 21051595)
Bio-markers for group separation (Class 2 and Metastatic): 22 significant variations (Few are chr16_g.69373414T>C, chr21_g.46330674C>A, chr19_g.46281745A>G, chr12_g.65141588C>T)
Clinical Variation Gene/Protein Expression
© Interpretomics www.interpretomics.co 8
Omnia contains curated Omics data (Variation, Expression, GO, Pathway, Drug, and Pharmacogenomics) along with subjects’ clinical data such as Demographics, Environmental, Phenotype and other attributes
Curation is based on Data mining and Text mining techniques using Manual curation and Manual validation pipelines by PhD quality biologists
Fields in Omnia are populated based on controlled vocabulary like HGNC, OMIM, UMLS, ICD10, and MeSH terms
Omnia contains 316 disease types for four disease groups: Neurology, Metabolic, Paediatric, and Oncology
Currently, Omnia contains more than 200,000 Variations, 100 Genomic experiments and 5000 Curated papers for Genotype-Phenotype relationships
© Interpretomics www.interpretomics.co 9
Omnia KB
Variation
Expression
Gene Ontology
Pathways
Drug
Pharmacogenomics
External DatabasesExAC, ESP, dbSNP, SRA, COXPRESSdb,Recon X, UMLS, Reactome, GEO, GO consortium, Drug Bank ....
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Forecast of Omnia
High-throughput Experiments
Omnia – Knowledge Base
Summary
Best-in-Class solution with analytical platform and knowledge base for biomarker discovery
Support for every stage of the drug development process using big data analytics Contains multi-omics multi-scale data in the knowledge base Genome-phenome and Phenome-genome modeling Supports multi-experiment type
- Features
- Benefits
© Interpretomics www.interpretomics.co 10
Identification of Right Target and Right Patient Reduced Cost and Improved TAT (Turn around time) Increased success rate of drug discovery
Corporate Office: India Corporate Office: USAInterpretOmics India Pvt. Ltd., InterpretOmics, Inc.#15 Shezan Levelle, Walton Road #5 Parker Street, LexingtonBangalore – 560 001 MA 02421, USAEmail: [email protected]: +91 80 46623 800 Telephone: 415-800-4515URL: www.interpretomics.co URL: www.interpretomics.co
Genomic Sequencing Lab: IndiaInterpretOmics Center for Next Generation Sequencing#329 7th Main, 80 Ft Road, Indiranagar, HAL II StageBangalore – 5600 08/
Thank You