2. omics and bioinformatics

What is the genome

• full set of DNA including all genes and non-coding regions

• Information required for development, function and reproduction

What is the epigenome

• complete set of chemical changes to DNA (e.g. methylation) and his tone proteins (e.g. acetylation) that regulate gene expressions without altering the dna sequence

• Dynamic and responsive to environmental, developmental, and lifestyle factors

What is the transcript or

• Complete set of RNA molecules including mRNA, non-coding RNA transcribed from the genome at a specific time or condition

• Reflects gene activity and used to study gene expression patterns in different tissues or diseases

What is the proteome

• Entire set of proteins expressed by genome, cell, tissue

• Includes isoforms and post-translational modifications (e.g. phosphorylation, glycosylation)

What is the metabolism

• consist of metabolites (e.g. amino acids, lipids, sugars)

• End products of cellular responses, showing physiological and biochemical state of an organism

Difference between the genome and other “omes”

Genome is static whereas other omes are dynamic

Omes interact with the genome - shifting, adapting, pools of cellular components

The genome is the basic set of instructions from which the gene products are derived

The genome can inform if there is a malfunction

What is a genomic bio marker

Measurable DNA or RNA characteristics that’s an indicator of normal biological, pathogenic process and/ or responses to therapeutics

• Doesn’t include proteins or metabolite

How does genomic data contribute to drug target identification and understanding patient variability

• Genomic analyses can reveal mutations, gene amplifications, or single nucleotide polymorphisms (SNPs) associated with disease susceptibility or drug metabolism

• E.g. pharmacogenomics use this to predict adverse drug reactions or tailor therapies based on genetic makeup

Give the 4 timeline aspects of the human genome project

1. 1996: HPG leaders share data - public ally available

2. 1998: cellera (private funding) formed to sequence genome

3. 2003: 92% HG sequences

4. 2022: remaining 8% HG sequenced

6 goals of the genome project

1. identify all 20,000-25,000 approx. Genes in human DNA

2. Determine the sequences of chemical boiling point that make up DNA (high throughout sequencing)

3. Improve tools for data analysis

4. Store this information in data bases (bioinformatics)

   • improve content and use

   • Develop better tools for data generation, capture and annotation

   • Develop and improve tools for functional studies

5. Transfer related technologies to private sector (e.g. AstraZeneca)

6. Address the ethical, legal, social issues

Name 4 genomic browsers

1. NCBI

2. Ensemble

3. GenomeNet

4. UCSC

5 ways in which genomics can be used in drug discovery and development

1. Understanding disease mechanisms

   • insights mainly into monogenic diseases

2. Understanding biology of infectious agent

   • insigh into therapeutic target and info about drug resistance in these microorganisms

3. Identifying potential drug targets

   • gene variants assocKate’s

4. Validating drug targets

   • transgenic and knockout mice to validate function

5. Assay development for selected drug targets

Epigenome; how does modification of chromatin structure influence gene expression

• His tone variants

• Post- translational modifications of amino acids on amino terminal tail of hsitomes

• Covalent modifications of DNA bases

What roles does the epigenome play in therapeutic discovery and response prediction

Epigenetic changes can activate or silence genes involved in disease progression (e.g. tumour suppressor genes in cancer).

Drugs targeting epigenetic regulators (like dna methyltransferase inhibitors or his tone deacetylase inhibitors) can reverse abnormal gene expression patterns

Why is the transcriptome important in drug discovery

• Target validation to determine differences between healthy and diseased cells exposed to stress/toxin/etc

• Helps identify unregulated or down regulated genes

How does proteomics contribute to drug development and bio marker identification

• Useful to determine drug mechanism of action and target

• Enhanced understanding of disease mechanism

• Informing assay development for screening of leads

• Identifying bio markers as surrogate endpoints for efficacy, toxicology and disease stratification

What is the most common proteomics method

bottom up proteomics

• Protein sample digested using trypsin into skallmpeptidesn

• Peptide separation using liquid chromatography (LC-MS)

• Peptide analysis with mass spectrometry: abundance and protein sequencing

What is the role of metabolism is in drug discovery

• Drug safety

• Clarifying disease processes

• Generations of new biomarker

• Bridging gap between human and animal studies

What is bioinformatics

Creation, analysis and management of information about living organisms

Computational tool

Why is bioinformatics large data

• Data sequencing full genomes

• Amino acid sequences of proteins

• 3D structures of proteins

• Nuclei acids

• Omicsmdata

2 major models of bioinformatics application

1. Query

   • like search e.g. nucelotide sequence used to find similar sequence in other organism

2. Data mining

   • hidden patterns

What is data mining

Sample set

• Clustering technique: hierarchy

• Sequencing alignment and pattern: BLAST

• Biological network analsys: KEGG, stringab

What does data mining algorithm tell you

• Association of corrrelations

• Prescience of subgroups : clustering samples into classes

• Variables can b eased to classify a new sample into class

• Mathematical or logical functions e.g. regression analysis

Problems of data mining

• Too much info : complex computational methods to pull out relevant info

• Too little data: data too sparse to apply parameters leading to incorrect prediction or results