Download Slides

Living on the Edge (of
Translational Informatics)
Opportunities and Challenges
for Integrating Bioinformatics
into the Clinical Realm
Russ B. Altman (Stanford U.)
Samuel Volchenboum (U. Chicago)
Robert R. Freimuth (Mayo Clinic)
Casey Overby (Johns Hopkins)
Subha Madhavan (Georgetown)
Lewis Frey (Medical U. of South Carolina)
Jessie Tenenbaum (Duke)
Goals
•Review trends in integrating bioinformatics
into clinical care
•Focus on interfaces: tools, systems,
processes for bench to beside translation
•Broad range of issues from basic informatics
systems for clinical data analysis to issues of
ethics and patient engagement.
Process
1. A brief journal club review of 1-2 publications
that set stage for speaker. These have been
chosen by speaker, and will be presented in
abbreviated fashion.
2. Speaker will present on relevant topic (30
minutes)
3. If not DONE, loop to (1.)
Volchenboum:
Informatics techniques
used in clinical
practice
“Detection of Circulating Tumor DNA in Early- and
Late-Stage Human Malignancies” (Bettegowda et
al, Sci. Trans. Med, 2014)
• Goal: Develop new methods to detect and
monitor cancer.
• Method: Digital PCR to detect circulating tumor
DNA (ctDNA) in 640 cancer patients.
• Result: ctDNA was detected in 82% of patients
with metastatic non-brain tumors and 55% of
localized tumors.
• Conclusion: ctDNA is broadly applicable, and
shows promise as significant biomarker for
clinical cancer management.
24553385
Sequencing Clinical Assay for Solid Tumor
Molecular Oncology” (Cheng et al, J. Mol. Diag,
2015)
• Goal: Develop Next generation sequencing
(NGS) method for assessing mutational status
on key cancer genes.
• Method: “Capture” technology for panel of 341
cancer genes (from formalin-paraffin samples).
• Result: Able to detect most known mutations in
284 samples and 48 exons, including SNPs,
indels, copy number alterations, structural
arrangements.
• Conclusion: NGS can provide reliable
25801821
Freimuth: Utilizing
genomic data in
clinical systems
“Standards and guidelines for the interpretation of
sequence variants: a joint consensus
recommendation of the American College of
Medical Genetics and Genomics and the
Association for Molecular Pathology” (Richards et
al, Gen in Med, 2015)
• Goal: Create standards for communicating
information about sequence variants.
• Summary: Specific definitions for “pathogenic,”
“likely pathogenic,” “uncertain significance,”
“likely benign,” and “benign” + evidence levels.
• Conclusion: ACMG made important
contribution by creating discrete codes and
25741868
Overby: Increasing the
reach of clinical
genomics research
and
genomics-informed
care
“Convergence of Implementation Science,
Precision Medicine, and the Learning Health Care
System: A New Model for Biomedical Research”
(Chambers et al, JAMA, 2016)
• Goal: Describe the great opportunities with
convergence of data from omics, wearables,
EMR.
• Summary: Learning healthcare system will
bring ongoing systematic improvement of
medicine. Implementation science studies best
practices in the translation of research into
practice.
• Conclusion: The triad of implementation
science, precision medicine and learning27163980
health
Madhavan: Practical
Precision Medicine:
Integration of clinical
and
genomic data to
support cancer care
“The cancer biomarker problem” (Sawyers,
Nature, 2008)
• Goal: Identify chief barriers to identifying useful
biomarkers for assessing drug response.
• Summary: Describe prognostic and predictive
biomarker types for cancer. Review challenges
in discovery and commericialization.
• Conclusion: Biomarker discovery and validation
is expensive and should be done through
public-private collaborations.
18385728
Frey: Collection of
data for research
“The immortal life of Henrietta Lacks” (Skloot &
Bahni, 2010)
• Goal: Tell the story of HeLa cells, how they
were derived and used, and the story of the
family of Henrietta Lacks, from whom they were
derived.
• Summary: There was no culture of informed
consent for research purposes, cells potentiated
much valuable science, patient and family were
not aware.
• Conclusion: We need to do better in engaging
patients as informed participants in science.
No PMID = Book
Tenenbaum: Ethical,
legal, and social
implications of
genomic testing
“23andMe, the Food and Drug Administration, and
the Future of Genetic Testing” (Zettler et al, JAMA
Int. Med, 2014)
“23andMe and the FDA” (Annas & Elias, NEJM,
2014)
•Goal: Discuss FDA letter to Direct-to-Consumer
genetic testing asking it to cease/desist.
•Key argument: When reports for high disease
risk of 3 DTC companies were compared, they did
not match.
•Summary: A milestone, since it ended the FDA’s
silence on genetic testing regulation, and signalled
more involvement in quality control of genetic
24535082 & 24520936
testing.