Summary
Summary BMS 38 Biomarkers notes
- Course
- Institution
Notes from all the lectures
[Show more]
Seller
Follow
kleopatratzai
Content preview
BIOMARKERS............................................................................................................................1BIOINFORMATICS......................................................................................................................9
MASS SPECTROMETRY............................................................................................................16
NEXT GENERATION SEQUENCING...........................................................................................25
BIOMARKERS
1. Biomarkers in the pharmaceutical industry
Personalized medicine in melanoma. The first event that occurs in the benign nevus stage is
a BRAF mutation. Other tumor suppressive events can be arrest of the cell cycle, break or
inactivation. Some proteases are then increased or lost. BRAF is a kinase.
- Phosphorylation is not needed, kinase always active and always phosphorylates MEK
and ERK cell constantly grows
- B-RAFV600E (mutation in valine) cells always grow and become cancer cells
- RAF inhibitors will block pathway, block cell growth and inhibit cancers (in mice) that
have a B-RAFV600E mutation
- 60% of melanoma patients have B-RAFV600E mutation
- Basis for a personalized medicine!
B-RAF identified as a human oncogene, marker for melanoma Development of
Vemurafenib.
Biomarkers: a characteristic (gene, protein, compound in blood etc.) that is objectively
measured and evaluated as an indicator of normal biological processes, pathogenic
processes, or pharmacologic responses to a therapeutic intervention.
Pharmaceutical developments target discovery, lead discovery, lead optimization,
exploratory development.
, 2. Biomarkers in academic research and healthcare
Case study:
- Healthy parents two deceased children
- No mutations in the OXPHOS complex I-V
- Whole exome sequencing mutation in WARS2 gene
- WARS2 is mtDNA-coded tryptophanyl-tRNA synthases
- Novel mutation causes instability of WARS2 protein
- Less charging of Trp-tRNATrp
- New prenatal genetic test!
Lessons
- Technology innovation is driving impact in personalized healthcare
- Crucial to combine different molecular views to understand human health and
disease (X-omics) Fast translational of biomarker research to implementation
needed.
21000 genes 1000000-2000000 protein forms.
Glycosylation: addition of a sugar molecule usually on asparagine that has an effect on
structure, stability, interactions, transport and activity. Proteins can have multiple
glycosylations. Each glycosylation site can have multiple glycans. High number of
combinations. Proteins can be differential expressed.
Power of omics: rather tha referring to a single biomarker you refer to a panel with
standardized platforms higher diagnostic yield, contextualization of change.
, 3. Biomarkers in personalized (health)care
A molecule in a cell has an effect on another
molecule in another cell. People are more than
linear pathways. Different genetic make-ups and
lifestyles, environments, risk factors and
preferences.
Digital biomarkers
Definition: ‘Digital biomarkers are objective, quantifiable, physiological, and
behavioral measures that are collected by means of digital devices that are portable,
wearable, implantable, or digestible’
Definition: ‘Non-invasive, sensitive digital biomarkers offers the opportunity to
support monitoring of disease progression through capturing dynamic fluctuating
symptoms at home in the patient’s lived environment. Digital health technologies
may also reduce patient and site burden and enable engagement of more diverse
populations including rural environmental settings’.
Advantages digital biomarkers
- Continuous monitoring versus 1 snapshot observation
- Real world data versus data from clinically controlled circumstances
- More comprehensive and rich data sets
- Truely personalized
- Strong potential in molecular + clinical + digital + environmental biomarkers for
optimal insight in complex biological systems
- Better basis to drive Personalized health(care)
- Better support for phase 1, 2, 3, 4 clinical trials
4. Biomarker innovation gaps
Elevated levels of IL-8 in melanoma patients study that confirms these levels develop
IL-8 assays for clinical use.
- IL-8 appears to be sensitive to freeze-thawing.
- Tumor load might have been too low.
- There is tumor heterogeneity.
Vemurafenib shows strong initial effects but there is emerging drug resistance.
Biomarker levels I tissue vary. Also in body fluids.
3 translational innovation gaps.
- research to research
- research to diagnosis
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller kleopatratzai. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $7.65. You're not tied to anything after your purchase.
Can Stuvia be trusted?
4.6 stars on Google & Trustpilot (+1000 reviews)
56326 documents were sold in the last 30 days
Founded in 2010, the go-to place to buy study notes for 14 years now