Lec 16- biomarkers Flashcards
1
Q
Biomarkers
A
- A measurable indicator of a biological state
- Focus on molecular biomarkers that can be used to charactise
- Normal biological process- define normal levels
- Pathogenic processes- variation from normal levels can indicate a certain pathology
- Pharmacologic responses to a therapeutic intervention- biomarker can indicate efficacy of the intervention
- E.g. Hba1C- if high = diabetes, lowering = good diabetic control
2
Q
Describing cancer- staging
A
- Staging of cancer 0-4
- Stage 0- no evidence- non-invasive
- Stage 1- small tumour with no spread to local LN (lymph nodes)
- Stage 2- based on size or spread to LN
- Stage 3- based on size and pread to local or more distant LN
- Stage 4- Fully metastatic spread to distant parts of the body
- TNM: Tumour, LN, Metastais’ is a different method of staging
3
Q
Metastatic cancer picutres
A
- MRI
- PET
- CT scan
- Ab linked to x-ray emitter- then x-ray
- All of these are expensive, require specialists to diagnose
4
Q
Techniques for measuring biomarkers
A
- Non-invasive
- Breath, urine, stool
- Invasive
- Tissue biopsy, blood
- Measure DNA, lipids, metabolites, proteins- identify a pattern that is different between pathological and normal states
- Identify where the cancer is, type of cancer and so the best course of action in terms of treatment- this is personalised precision medicine
5
Q
Molecular biomarkers
A
- Genetic profile- genome
- SNPs
- miRNA levels
- mRNA levels
- Protin fragment
- Protein modification
- Protein abundance
- Lipids
- Metabolites
- Found in urine => plasma => tissue
6
Q
Capillary electrophoresis- mass spectrometry
A
- Separation- electrophoresis
- Measurement/Identification- MS
- Bioinformatic analysis
- Biomarker identification
7
Q
Raw data plot of CE-MS run
A
8
Q
Biomarker changes
A
- You can compare healthy graphs and those with disease
- The different disease states will have slightly different looking graphs = diagnostic tool
- Different biomarkers, different intensitys can not only identify kidney disease but differentiate between 3 different disease states
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9
Q
Disease classification by support vector machines
A
- Increased correct classification
- in 2 dimensions
- Separating, non-linear hyperplane
- In n dimensions
10
Q
Identification of markers
A
11
Q
Potential biomarkers for bladder cancer
A
- This is telling us what stage the bladder cancer is independent at which markers predominate in certain patterns
- Different levels of the different markers can indicate the stage of the cancer
- NB- these occur even when the cancer is asymptomatic- which stage they are in where affects treatment, as well as informing on prognosis
12
Q
Assessment of multiple diseases in one sample
A
- Biomarker for transplantation
- Biomarker for CMC reactivation
- Biomarker for graft rejection
- Biomarker for chron. renal disease
- In one sample screening for multiple different biomarkers for a range of indication- potential to start catching diseases at an earlier opportunity
13
Q
Mass spectrometric tissue imaging
A
- Lots of peaks- in terms of mass which represent molecules within which represent a molecule
- We look for patterns of peaks
- ATM this is post-mortem
- This would be more useful than histological measures because they require that we look at single molecules at a time
14
Q
HTN in rat kidney
A
- Comparison of kidney from wild type (WKY), stroke prone spontaneously Hypertensive (SHRSP), and a congenic strain with a mapped chromosomal loci responsible for HTN (8 weeks, salt dosed)
15
Q
Ab microarray
A
- This allows us to measure 1000’s of proteins simultaneously
- Also allows us to identify any modifications to those proteins (phosphorylation etc)
