DD: Lesson 13: Introduction to bioinformatics - the human genome project - target selection

Define genome

A whole set of genes plus all the DNA between your genes

How many base pairs does each cell contain?

3 billion base pairs

Define genomics

The study of the whole genome and how it works

What is the percentage range for genes that code for DNA?

1% - 2%

How many base pairs can a single gene have?

Hundreds or millions of base pairs

What does genes make?

Proteins

How many genes do humans have?

23,000 genes

How many genes do rice have?

41,000 genes

How many genes does bread mould have?

10,000 genes

How many genes does chicken pox virus have?

70 genes

What is bioinformatics?

A multi-disciplinary area that integrates biology with informatics, computer science and mathematics

When did bioinformatics occur?

In the 60s and 70s

What is the role of bioinformatics?

De-code DNA

When did the human genome project start?

1990

When did the human genome project end?

2003

How much did the first genome cost?

£2.7 billion

What did the human genome project do for the first time?

Make the human genetic blueprint completely readable

What did the human genome project discover?

See which genes cause diseases

What did the human genome project allow?

For genetic diagnostics to progress

How many nanometres is each nucleotide?

0.33

How many nanometres is the space between a double helix?

2.2 - 2.6

How many nanometres is a banana's diameter?

40,000,000

What is sequencing?

Reading the human genome letter by letter

How long does it take to read DNA today?

Less than a day

How much does it cost to read DNA today?

£1000

What happens to cells?

They are sampled/genome

What happens to these samples?

They are fragmented

What happens after the fragmentation?

End repair/adaptor ligation

How many copies are made off the adaptor ligation?

Thousands of copies

What happens to the thousands of copies?

Genomic samples into sequence machine

What happens to the data after the sequencing machine?

A bioinformatic analysis is done on the data

What does whole genome sequencing provide?

A high resolution, base by base

What types of variants are captured using genome sequencing?

1) Large variants
2) Small variants

What does whole genome sequencing identify?

Potential causative variants

What can be done is there might be other variants?

Further follow up studies of gene expression and regulation mechanisms

What does whole genome sequencing deliver?

Large volumes of data in short amount of time

What does whole genome sequencing support?

The assembly of novel genomes

How were volunteers recruited?

In a blinded process

What is the percentage range of human DNA sequences being near identical to other people?

99.6% - 99.9%

What is the percentage range of genomic differences between humans?

0.1% - 0.4%

What is the ancestry of most of the genomes sequenced?

European

How many genomic variants re there in each individual?

10 million

What are the 3 impacts of the genomic variants in terms of disease risk?

1) Increases the risk of disease
2) Has no effects on disease risk
3) Decreases the risk of disease

What is the most aggressive form of breast cancer?

Triple negative breast cancer

What is triple negative breast cancer also known as?

TNBC

Who are more likely to be diagnosed with TNBC?

Black women

What link is there to genetic variation and TNBC?

Genetic variation contributes to predisposing some women to aggressive cancers

What is differential gene expression?

Differences in abundance of gene from one cell to another or one person to another

What are the 5 ways the human genome project has helped?

1) Precision medicine in cancer and other diseases
2) Undiagnosed diseases
3) Rare diseases
4) Molecular biology research
5) Variations between closely related species

What are the 5 reasons genomes are sequenced?

1) To create a reference genome
2) To do comparative studies
3) To understand how a species responds to changes under drug pressure
4) To understand how species diversify
5) To understand how species are related

What are the 2 reasons the human reference genome is always being modified?

1) Many repeated and long regions weren't sequenced
2) It wasn't diverse enough

What needs to be done every time a genome is sequenced?

Align it to the reference to see if it matches

By 2035 how many babies will get whole genome sequencing at birth?

650,000

By 2035 what will genomics underpin?

Early diagnosis and interventions

By 2035 what will happen to cancer?

1) Early cancer detection
2) Cancer treatment stratification and monitoring

What is pharmacogenomics?

Give people the right drugs at the right time

What are the 3 reasons bioinformatics is used in healthcare?

1) Uncover the differences in people's genetic makeups
2) Personalised medicine
3) New classifications

How does bioinformatics make new classifications?

They move from traditional phenotype to genotypic characteristics

What are the 5 stages of the drug development pipeline?

1) Basic research
2) Lead discovery
3) Preclinical development
4) Clinical development
5) FDA filing

How many years does lead discovery take?

3 years

How many years does preclinical development take?

1 year

How many years does clinical development take?

6 years

How many years does FDA filing take?

1.5 years

What occurs in basic research?

Target ID and selection

What occurs in lead discovery?

Candidate selection

What occurs in preclinical development?

IND filing

What occurs in clinical development?

NDA filing

What research is used in target selection?

Academic research

What companies also do target selection?

Pharmaceutical companies

What is a drug target?

A molecule in the body that is associated with a particular disease process

What are drug targets usually?

Proteins

What are the 5 reasons drug targets occur?

1) Mutations
2) Insertions
3) Deletions
4) Chromosomal translocation
5) Epigenetic changes

What are the 2 reasons why drugs fail?

1) Due to efficacy
2) Ineffective target selection and validation

Where is DNA/RNA or proteins extracted from?

Different cell types

What is performed on DNA and RNA?

DNA/RNA sequencing

What is performed on protein?

Proteomics

What does bioinformatics do to DNA, RNA sequencing and proteomics?

Identify differential gene/protein expression

Give 6 examples of a gene/protein list

1) P53
2) HER2
3) MUC1
4) EPCAM
5) CD24
6) ALDH1

What does the gene and protein list identify?

Novel compounds against target