Introduction to Bioinformatics - Part 2 Flashcards
What causes cancer?
Damage to our DNA / genes
- Natural accumulation of DNA damage (cancer occurs more often in older people)
- Exposure to factors that damage DNA (eg: UV, smoking)
- Inheriting faults in genes that increases risk of developing cancer
Does all DNA damage cause cancer?
No
Damage to certain genes, so called cancer driver genes, contribute to cancer
How do we identify what went wrong in cancer genome?
Compare DNA of cancer cells to DNA from healthy cells
To understand cancer, can look for association of genetic and genomic factors with what?
human health and disease,
their prevalence within families and populations,
their interactions with environmental factors,
and their contribution to disease risk.
Studying genetic and genomics may help to…
.) diagnose the disease
.) predict how severe the disease might be
.) choose the best medicine and correct dose
.) could find genetic factors that could be passed on to the next generation
What change is often found in the cancer genome?
Aneuploidy- quantity of genome changes
DNA& RNA sequencing is the process of what?
Determining the precise order of nucleotides within a DNA & RNA molecule
What four bases is DNA composed of?
Adenine, guanine, cytosine, and thymine (A,G,C,T )
What four bases if RNA composed of?
Adenine, guanine, cytosine, and uracil
A,G,C, U
What do NGS technologies facilitate?
Massively Parallel Sequencing
- multiple sequencing reactions are running simultaneously
What are the predominant applications of whole genome sequencing?
Structural variants
Point mutations
Copy number variation
What are the predominant applications of whole exome sequencing?
Point mutations
Copy number variation
What are the predominant applications of PCR amplicon?
Point mutations
Deletions
What are the predominant applications of transcriptome RNA?
Gene expression
Gene fusions
Splice variants
What are the predominant applications of exon capture transcriptome?
Gene expression
Gene fusions
Splice variants
- What is single cell sequencing?
2. What is advantage of this?
- Tissue first separated into individual cell
Cells then sequenced separately. DNA methylation, Intracellular protein etc can be measured
- Allows specific investigation of molecular landscape of cells
What are the four steps of NGS workflow in clinical oncology?
- Sample processing
- Data processing
- Variant calling and annotation
- Data utilisation
What is MSK?
Gene panel used
Overall analyses up to 500 genes – genes are nominated by researchers and experts across MSK (Memorial Sloan Kettering). Are all actionable targets, aim is that gene list is updated to include new genes in this panel.
Capable of detecting several classes of genomic changes
Provides comprehensive picture of full spectrum of genetic changes in tumour
What are the 8 steps involved in MSK?
- Patient consent
- Sample accessing
- Sample preparation
- Sequencing
- Bioinformatic analysis
- Case review and sign out
- Genomic variant database e.g OncoKB used to compared variants found
- Findings used for clinical report, clinical trial matching and data mining and interpretation
One example of bioinformatics is Foundation medicine gene panel
What are the tests available?
FoundationOne CDx-
- For all solid tumours
- Uses a tissue sample (tissue biopsy)
- Tests the DNA of over 300 genes
Foundation Liquid CDx-
- For all solid tumours
- Uses a blood sample (liquid biopsy)
- Tests the DNA of over 300 genes
FoundationOne Heme-
- For blood cancers and sarcomas
- Uses a tissue or blood sample
- Tests DNA of over 400 and RNA of over 260 genes
What does the FDA approve for adults and children with TMB-H solid tumours?
Pembrolizumab
What does Tumor mutational burden (TMB) refer to?
Number of somatic gene mutations present in a tumour.
What is TMB-H (high) defined as?
TMB ≥10 mut/Mb.
What is an alteration in the nucleotide sequence of the genome of an organism or a virus called?
MUTATION
