18. Future of Genetics Flashcards
integration into clinical care is severely challenged by …
a lack of accurate interpretations of the vast amount of human genetic variation known to exist
challenges to single gene testing
locus heterogeneity: a mutation in one of several genes may lead to a clinically similar disease
incidental results
genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance
why are most cancers not screened for
because their prevalence in the general population is too low to justify screening programmes on an individual cancer basis
in what situation could you screen for cancer tests
should multiple cancers be effectively screened for in a single test this would alter this calculation
what is the essential to this proposed cancer screening
the success of this approach is the sensitivity and specificity of the classifier which determines whether the test result is normal (non cancer) or abnormal
what is the best biological matrix to look for early signs of cancer
- tumours can secrete small fragments of DNA called circulating tumour DNA (ctDNA), into circulation where they are found in plasma
- because all cells in the body have access to the circulatory system, blood is an attractive analyte for a cancer test
- a “liquid biopsy” using blood samples obtained from cancer patients could detect the characteristics of ctDNA that may have prognostic and/or therapeutic implications
problem with the biological matrix to look for early signs of cancer
with mutations found in ctDNA, circulating in the blood it is difficult to say where the mutation comes from (tissue of origin)
how may epigenetics offer a solution to this problem
each tissue has a characteristic epigenetic pattern
how does preparing DNA methylation help determine the tissue of origin of a cancer signature in the blood
- each tissue has a different pattern of fingerprint of DNA methylation
- alterations in DNA methylation are common in a variety of tumors are considered to be among the earliest and most comprehensive genomic aberrations occurring during carcinogenesis
DNA methylation’s relation to cancer
DNA methylation has long been regarded as a hallmark of cancer and holds great promises for early-stage cancer detection
comparing methylation patterns from an individual blood sample …
has the potential to be used to screen for early signs of a variety of different cancers
is early screening ready for clinic
- Grail a sequencing company is pioneering the use of ctDNA in blood for the early detection of 50 different types of cancer
- the NHS is set to initiate the trial of Galleri blood test
- the pilot will enroll over 150,000 participates to examine the tests clinical utility
Variant of Unknown significance (VUS)
a genetic alteration whose association with disease risk or health impact is not clearly established
Clinvar
a database containing genetic variations classified for diseases and drug responses, with supporting evidence
where do the submissions in ClinVar come from
over 90% come from clinical labs and represent a glimpse of the state of variation being observed in patients
how can the biological and clinical impact of genetic variants be predicted at scale
- computational predictive modeling
- bioinformatics tools
- database comparisons
explain bioinformatics tools
use of software that predicts the impact of genetic variants on protein structure and function
explain database comparisons
compare the variant against databases that catalog known disease-associated and benign variants
what is the biggest challenge VUS predicts
many of these VUS arise due to missense variants
- missense variant results in the sibstitution of one amino acid for another in the protein
- this change can affect the protein’s structure and function, depending on where the change occurs and what amino acids are involved
why might you combine genetic data with other types of data
when genetics isn’t enough
by integrating genetic information with various other data types - such as clinical, environmental and lifestyle factors: genetic data can contribute to a comprehensive overview of an individual’s health status and potential future health trajectories
GMAI
Generalist Medical AI
- broad and comprehensive AI system designed to perform a variety of tasks across the medical and healthcare fields
- GMAI model aims to be more versatile and wide-ranging in its capabilites
GMAI features
- multi functionality
- decision support
- patient interaction (through chat boxes or virtual health assistants)
- training and education (provide simulation-based learning environments)
what does NGS based Genomic testing offer
increased diagnostic reach over single gene testing and allows for translational research and new discoveries
what can cell free DNA offer
great potential for the early detection of cancer
