Precision oncology relies on targeted drugs such as kinase inhibitors that are presently administered based on molecular profiles obtained from surgical or bioptic tissue samples. The inherent ability of human tumours to molecularly evolve in response to drug pressures represents a daunting diagnostic challenge. Circulating free DNA (cfDNA) released from primary and metastatic lesions can be used to draw molecular maps that can be continuously updated to match each patient’s tumour evolution, in order to help with the clinical-decision making.

Learning Objectives

• Improve personalized medicine for cancer patients based upon detailed and complete molecular characterization of each patient’s tumor.
• Employ liquid biopsy analysis in clinical settings.
• Adapt clinical treatment of cancer patients to the tumor evolution under different treatment regimens.

Duration: 0.75 hr

Level of Instruction: Basic

Recording Date: August 3, 2017

Molecular testing using high-throughput sequencing technologies is becoming a common practice for personalized care of patients with cancer. Rendered interpretation of detected variants in an oncologic molecular assay has a significant impact on tumor diagnosis, choice of therapy and risk stratification. However, the rate of identification of novel and rare variants by high-throughput sequencing outpaces our current understanding of the cancer genome and available variant databases. As a result, there is a lack of a standardized approach to interpretation of somatic variants. In January 2017, a joint consensus of a working group comprised of members from the Association for Molecular Pathology (AMP), College of American Pathologists (CAP) and American Society of Clinical Oncology (ASCO), published the guidelines for the interpretation and reporting of somatic variants. This talk will discuss the fundamental informatics concepts of variant interpretation and reporting in the context of this recent guidelines.

Learning Objectives

• Apply the recommendation from the recent joint consensus (AMP, ASCO, CAP) guideline for interpretation and reporting of somatic variants in clinical cancer testing.
• Employ appropriate informatics strategies for optimized annotation of sequence variants to ensure accurate variant interpretation.
• Review and identify limitations of public and proprietary genome and variant databases before incorporation into bioinformatics pipeline for clinical use.

Duration: 1.0 hr

Level of Instruction: Basic

Recording Date: August 23, 2017

The human gastrointestinal microbiome “differentiates” during infancy and childhood in terms of microbial composition and function. Microbial function is relatively conserved compared to microbial composition. Children have greater relative abundances of microbial genera such as Bifidobacterium and a greater genetic capacity to produce vitamins. The composition of the microbiome may affect relative susceptibilities to enteric infections, including recurrent C. difficile infection. Microbiome-based treatment modalities such as fecal microbiota transplantation may be necessary for successful treatment of disorders of microbial ecology. Differences in microbial composition and function may affect the course of functional bowel disorders such as irritable bowel syndrome. Finally the metabolic capacity of gut microbes may affect the pathology of inflammatory bowel disease via the production of anti-inflammatory metabolites. Diet, the microbiome and host genetics may have a profound impact on digestive disease phenotypes. Newer diagnostic approaches based on metagenomic medicine open new possibilities for diagnosis, stratification and treatment of patients with chronic gastrointestinal disorders.

Learning Objectives:

• Describe key differences in the functional capacity of the pediatric versus adult gastrointestinal microbiomes.
• State the difference(s) in microbial composition among individuals who suffer from recurrent Clostridium difficile infection.
• Describe features in the microbiomes of individuals with irritable bowel syndrome, responding to dietary interventions.
• State basic mechanism(s) explaining how gut microbes reduce chronic intestinal inflammation.

Duration: 1.0 hr

Level of Instruction: Intermediate

Recording Date: September 19, 2017

Over the last decade, next-generation sequencing (NGS) has transformed the field of clinical genetic testing. Interpretation of genetic variants in a constantly evolving technology environment continues to be increasingly complex given the dramatic increase in the size of datasets. This requires clinical laboratories to be increasingly vigilant about the adoption of technology and informatics algorithms used in the application of interpretation. Using case studies as examples, this lecture provides specific challenges related to variant interpretation in the context of NGS derived data. We will discuss potential solutions to address these complexities as well as best practices during development and validation of these techniques.

Learning Objectives:

• Describe the basic principles of an informatics pipeline
• Identify the different mechanisms by which interpretation of data can be affected.
• List the different approaches that can be used to address areas of complexities 

Duration: 1.0 hr

Level of Instruction: Basic

Recording Date: July 17, 2018