THE OMICS AND BIOINFORMATICS APPLICATIONS IN DRUG DISCOVERY

THE OMICS AND BIOINFORMATICS APPLICATIONS IN DRUG DISCOVERY: OVERVIEW AND Presentation. PROSPECTS At The PSN National Conference – Kaduna – 6/11/19 Cyril Onyemaechi Aninwike • B. Pharm (Nig); PGD (Mktg–Nig); M. Sc (Mgt–Nig), Ph. D [Mgt– Nig (in view)]

Complex, risky and PRIMER rewarding sequential process of drug discovery. Drug Discovery and Development This process is difficult, expensive and highly competitive. Requires human, financial, technological capital and regulatory adherence

Effects… • Failure to make the market • High cost of drug research and development Panacea… • Bioinformatics • Pharmacogenomics

OMICS • Studies genetic polymorphism and genetic effects on drug response for optimal drug selection, dose and treatment. • This is juxtaposed with the mortality effect of adverse drug reactions among patients with over $29 billion annual cost of medical errors (Rawlings, 2004; Prows and Prows, 2004). • This has led to a dearth of confidence in the health sector. 4

ELUCIDATING OMICS • English language neologism informally refers to it as field of Biology ending in omics – genomics, proteonomics, transcriptomics, metabolomics. • Instead, it is the collective technologies used in exploring molecular roles, relationships and actions within a cell. • Omics data enables the appreciation of disease etiology, druggable targets, demonstrating clinical efficacy. • By this, it is the pillar of systems medicine, and is integral to pharmaceutical research and development. 5

TYPES OF OMICS TECHNOLOGY S/N 1 a. TYPES Genomics Cognitive Genomics b. Comparative Genomics c. Functional Genomics Describes gene and protein functions and interactions (often uses trascriptomics) Metagenomics Study of metagenomes – genetic material recovered directly from environmental samples Neurogenomics Study of genetic influences on the development and function of the nervous system Pangenomics Study of the entire collection of gene families found within a given specie Personal Genomics Branch of genomics concerned with the sequencing and analysis of genomes, so genotypes can be compared with the published literature to determine likelihood of trait expression and disease risk. 6 d. e. f. g. DESCRIPTION Study of the genomes of organisms Study of the changes in cognitive processes associated with genetic profile Study of the relationship of genome structure and function across different biological species or strains

TYPES OF OMICS STUDIES S/N 2 TYPE Epigenomics DESCRIPTION Epigenome is the supporting structure of genome, including protein and RNA binders, alternative DNA structures, and chemical modifications of DNA Lipidome is the entire complement of cellular lipids, including the modifications made to a particular set of lipids, produced by an organism or a system. Large-scale study of the pathways and networks of lipids – using mass spectrometry techniques 3 Lipidomics 4 Proteomics Proteome is the entire component of proteins, including the modifications made to a particular set of proteins, produced by an organism or system. Proteomics is a large-scale study of proteins, particularly their structures and functions – using mass spectrometry 4 b. Proteogenomics An emerging field of biological research at the intersection of proteomics and genomics. 7 Proteonomics data are used for gene annotations.

TYPES OF OMICS STUDIES …cont’d S/N 5 TYPE Glycomics DESCRIPTION The comprehensive study of the glycome – sugars and carbohydrates 6 Foodomics A discipline that studies the Food and Nutrition domains through the application and integration of advanced –omics technologies to improve consumers’ well-being, health and knowledge 7 Transcriptomics Transcriptome is the set of all RNA molecules, including m. RNA, r. RNA, t. RNA, and other non-coding RNA, produced in one or a population of cells. Transcriptomics is therefore the study of transcriptomes – their structures and functions. 8 Metabolomics The scientific study of chemical processes involving metabolites. A systematic study of the unique chemical fingerprints that specific cellular processes leave behind 8

APPLICATIONS OF OMICS IN DRUG DISCOVERY • Quantitative integration of molecular network data to R&D. • Innovative capturing of disease pathological features to bridge clinical phenotypes using “disease-on-chip”. • Uses “disease-on-chip” to uncover molecular etiology, identify drug targets and reveal drug responses. • This has been successfully experimented on Alzheimer’s disease. 9

Omics Technology and Precision-Medicine-by-Design • Omics data can be leveraged for discovery of prognostic and predictive efficacy biomarkers for patient stratification and design of clinical trials. • Reduction of drug attrition via leveraging public knowledge bases of clinical incidence of adverse reactions, genomics, protein–protein interactions made available by big omics data. • Use of metabolomics to identify and quantify the metabolome for biochemically monitoring disease states and assessing drug actions. 10

Metabolomics • This paper describes metabolomics as an important tool in drug discovery, and also gives an overview of metabolomic process. • It is the quantitative assessment of the metabolic responses of a biological system to measure changes in metabolic response when exposed to genetic alterations. • Indicates interaction level between genome, proteome and the environment. • Displays information on metabolic and cellular processes. 11

BIOINFORMATICS AND DRUG DISCOVERY • “Bioinformatics is the application of computer systems to generate and clarify biological data. ” • OBJECTIVES • Efficient organization of vast reams of molecular biology data. • Develop tools for molecular biology data analysis • Accurate result interpretation 12

SPECIFIC APPLICATION OF OMICS TECHNOLOGIES • Oncology: Targeting aberrant pathways associated with mutated genes to gene therapy • Genetic disorders • Antibiotic development • Infectious Diseases: TB, Dengu Fever, Filariasis • Malaria genomics 13

Omics of Tuberculosis Pathogens and Host Responses • Tuberculosis (TB) leads to over 2 million deaths annually (W. H. O. , 2018 a) • Its mycobacterial genome was first sequenced in 1998 and enables genomic characterization, better diagnostic tools, drug susceptibility testing, and molecular epidemiology of circulating mycobacterial strains. • This has led to an improved control of TB.

Pharma cogeno mics Approa ch (Person alized Medicin e) • Design drugs that satisfy requirements of particular genetic sub-groups. • Reduce risk of adverse drugs effects. • Reduce the speculation in drug prescriptions • Ameliorate the use of multiple expensive drugs

BARRIERS TO OMICS AND BIOINFORMATICS IN DRUG DESIGN Still novel; thus less impact on… …rising cost of drug discovery …drug withdrawals from the market …lengthy approval periods

CHALLENGES/OPPOR TUNITIES IN OMICS AND BIOINFORMATION RESEARCH IN AFRICA. • Infrastructural deficit • Lack of Training Opportunities and Well-Structured Bioinformatics Courses • Limited Research Funding

CONCLUSION/PERSPECTIVES • Drug designing is very complex, • Though still at development expensive and time consuming stages, their potential is encouraging. • Bioinformatics provides a range • Both have aided of drug-related databases for understanding of drug designing and pathogenesis, for identifying development. prognostic and diagnostic markers. • Pharmacogenomics provides the genome level information about variable drug response. • Limited expertise in bioinformatics research and application.

URGENT REQUIRE MENT • Strengthen training and capacity building in Africa

• When the foundation is wrong, what can the Righteous Do? LAS T WO RD • In these days of Pharmacy Schools practicing “Alternative to Practical”…. . • WHAT HOPE FOR THE FUTURE OF OMICS AND BIOINFORMATICS IN DRUG DEVELOPMENT IN NIGERIA? ? ?

THANK YOU …Cy Aninwike