Posts Tagged ‘Medical genetics’

Genomics and Medicine: The Physician’s View

Genomics and Medicine: The Physician’s View

Author and Curator: Larry H. Bernstein, MD, FCAP


Genomics has had a rapid growth of research into variability of human genetics in both healthy populations in the study of population migration, and in the study of genetic sequence alterations that may increase the risk of expressed human disease.  This is the case for cardiology, cancer, inflammtory conditions, and gastrointestinal diseases. For the most part, genomics research in the last decade has shed light on potential therapeutic targets, but the identification of drug toxicities in late phase trials has been associated with a 70 percent failure rate in bringing new drugs to the market.   Despite good technologies for investigative studies, initial work is carried out on animals and then the transferrability of the work from a “model” to man has to be assured.  That is the first issue of concern.

Secondly, there is a well considered reluctance on the part of experienced and well prepared physicians to be “early” adopters to newly introduced drugs, with the apprehension that unidentified clinical problems can be expected to be unmasked.  It is, however, easier to consider when a new drug belongs to an established class of medications, and it has removed known adverse effects.  In this case, the adverse effects are known side effects, but not necessarily serious drug reactions that would preclude use.

A third consideration is the cost of drug development, and the cost of development is passed on to the healthcare organization in the purchasing cost. We can rest assured that the Pharmacy and Therapeutics Review Committee will not cease meeting on a regular schedule anytime soon.  Further, how do the drug failures become embedded in the cost of the pharmaceutical budget passed on to the recipient.  Historically, insurance is an actuarial discipline.  But in the lifetime of an individual, they are bound to see a physician for acute or chronic medical attention.  Only the timing cannot be predicted.  As a result, dealing with the valid introduction of new medications is a big concern for both the public and the private insurer.

How does this compute for the physician provider.  The practice of medicine is not quickly adaptive, as the physician’s primary concern is to do no harm.   Genomics testing is not widely available, and it is for the most part not definitive for diagnostic purposes as things stand today.  It may provide assessment of risk, or of survival expectation.  The physician uses a step by step assessment, using the patient and family history, a focused physical exam, laboratory and radiology, proceeding to other more specialized exams.  Much of the laboratory testing is based on the appearance in the circulation of changes in blood chemistry of the nature of electrolytes, circulating cells in the blood and of the blood forming organ, proteins, urea and uric acid.  They are not exquisitely sensitive, but they might be sufficient for their abnormal concentrations appearing at the time the patient presents with a complaint. What tests are ordered is determioned by a need for relevant information to make a medical decision.

The relevant questions are:

1. acuity of symptoms and signs.
2. actions to be taken.
3. tests that are needed to clarify the examination findings.

once a provisional diagnosis is obtained, referrals, additional testing, and medication orders are provided based on the assessment.

Where does genetic testing fit into this? At this point, it will only be used

  1. to confirm a restricted list of diagnoses that have a high association with the condition, and
  2. only with the participation of a medical geneticist, when
  3. profiling the patient and other members of the family is required.

10d0de1 Vitruvian Man by Leonardo da Vinci

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Elastin Arteriopathy: The Genetics of Supravalvular Aortic Stenosis

Reporter: Aviva Lev-Ari, PhD, RN


Supravalvular Aortic Stenosis Elastin Arteriopathy

Giuseppe Merla, PhD, Nicola Brunetti-Pierri, MD, Pasquale Piccolo, PhD, Lucia Micale, PhD and Maria Nicla Loviglio, PhD, MSc

Author Affiliations

From the Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy (G.M., L.M., M.N.L.); Telethon Institute of Genetics and Medicine, Napoli, Italy (N.B-P., P.P.); Department of Pediatrics, Federico II University of Naples, Naples, Italy (N.B-P.); and CIG Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland (M.N.L.).

Correspondence to Giuseppe Merla, PhD, Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, viale Cappuccini, 71013 San Giovanni Rotondo, Italy. E-mailg.merla@operapadrepio.it


Supravalvular aortic stenosis is a systemic elastin (ELN) arteriopathy that disproportionately affects the supravalvular aorta. ELN arteriopathy may be present in a nonsyndromic condition or in syndromic conditions such as Williams–Beuren syndrome. The anatomic findings include congenital narrowing of the lumen of the aorta and other arteries, such as branches of pulmonary or coronary arteries. Given the systemic nature of the disease, accurate evaluation is recommended to establish the degree and extent of vascular involvement and to plan appropriate interventions, which are indicated whenever hemodynamically significant stenoses occur. ELN arteriopathy is genetically heterogeneous and occurs as a consequence of haploinsufficiency of the ELN gene on chromosome 7q11.23, owing to either microdeletion of the entire chromosomal region or ELN point mutations. Interestingly, there is a prevalence of premature termination mutations resulting in null alleles among ELN point mutations. The identification of the genetic defect in patients with supravalvular aortic stenosis is essential for a definitive diagnosis, prognosis, and genetic counseling.


Circulation: Cardiovascular Genetics.2012; 5: 692-696

doi: 10.1161/ CIRCGENETICS.112.962860


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Genomics in Medicine – Establishing a Patient-Centric View of Genomic Data

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 12/13, 2013

Second  Annual
Genomics in Medicine
Establishing a Patient-Centric View of  Genomic Data
February 13-14, 2014 | San Francisco,  CA

Dr. Michael Christman, President and CEO of the  Coriell Institute for Medical Research, to Present “Using a  Patient’s Genetic Information in the Real World” at the Second  Annual Genomics in Medicine  Symposium

When  a patient needs a new prescription, it will be necessary for the  physician to quickly and securely access his/her genetic data to  understand drug efficacy prior to dosing. Who will patients and  doctors trust to store and interpret the data? Coriell and the CPMC  research study have defined several of the key barriers to  accelerate the adoption and routine use of genomics in medicine and  have proposed solutions that are generally  applicable.

Dr.  Christman is an expert in genetics and genomics, with a focus on the  integration of genome information into the delivery of clinical  care. In 2007, he joined Coriell and initiated the Coriell  Personalized Medicine Collaborative® (CPMC®), a research study  evaluating the utility of using the knowledge of genetics in  medicine. Prior to joining Coriell, he served as professor and  founding chair of the Department of Genetics and Genomics for Boston  University School of Medicine. There he led an international team of  scientists in one of the first genome-wide association studies using  the Framingham Heart Study cohort, published in Science magazine.  Dr. Christman received his bachelor’s degree in chemistry with  honors from the University of North Carolina, Chapel Hill, his  doctorate in biochemistry from the University of California,  Berkeley, and was a Jane Coffin Childs postdoctoral fellow at the  Massachusetts Institute of Technology.



Incidental Findings in Genomic  Medicine: The Debate and the Data
Robert C.  Green, M.D., MPH, Director, G2P Research Program; Associate  Director, Research, Partners Center for Personalized Genetic  Medicine, Division of Genetics, Department of Medicine, Brigham and  Women’s Hospital and Harvard Medical  School

Genomic Medicine Implementations for  Primary Care
Erwin Bottinger, M.D., The Irene and  Dr. Arthur Fishberg Professor of Medicine; Director, The Charles  Bronfman Institute for Personalized Medicine, Icahn School of  Medicine, Mount Sinai

Ethical Issues Related to the  Return of Incidental Findings in  Children/Families
Ingrid A. Holm, M.D., MPH,  Director, Phenotyping Core, Program in Genomics, Divisions of  Genetics and Endocrinology, Boston Children’s  Hospital


Reducing the Complexity of  Clinical Omics Reporting for Clinicians and  Laboratories   [Listen  to Podcast <http://www.chicorporate.com/click-thru/131500/?email=avivalev-ari@alum.berkeley.edu> ]
Jonathan Hirsch, Founder &  President, Syapse

Beyond Sequence: Integration of Full-Genome  Technologies for Personalized Medicine in the  Clinic
Raphael Lehrer, Founder and Chief Scientist,  GeneKey

Targeted NGS of Clinical Samples:  Overcoming the Challenges of Obtaining High Quality Data from Low  Quality DNA
Diane Ilsley, Ph.D., Marketing Manager,  Genomic Services, Asuragen
Sponsored  by:


Genome Sequencing in the Clinic:  Found the Variants – Now What?
Jennifer Friedman,  M.D., Associate Clinical Professor, Neurosciences and Pediatrics,  UCSD/Rady Children’s Hospital San Diego

The  Answer is There, but I Don’t Understand It: Solutions from the Front  Line
Vanya Gant, Ph.D., FRCP, FRCPath, Divisional  Clinical Director for Infection, The Department of Microbiology,  UCLH NHS Foundation Trust

Using a Patient’s  Genetic Information in the Real World
Michael F.  Christman, Ph.D., President and CEO, Coriell Institute for Medical  Research

Developing Clinical Sequencing Assays  at Einstein-Montefiore
Cristina Montagna, Ph.D.,  Associate Professor, Genetics, Albert Einstein College of  Medicine


Direct-to-Consumer Genetic  Testing: Balancing the Good and the Bad
Nazneen  Aziz, Ph.D., Director, Molecular Medicine, Transformation Program  Office, College of American  Pathologists

Crowdsourcing Genetic  Discovery
Nicholas Eriksson, Ph.D., Principal  Scientist, Statistical Genetics,  23andMe

Personal Genomics through Smart Digital  Media
Patrick Merel, Ph.D., Founder & CEO,  Portable Genomics

> Sponsored Presentation  (Opportunities  Available
<http://www.triconference.com/click-thru/127354/?email=avivalev-ari@alum.berkeley.edu> )

The Ethical and Social  Implications of Direct-to-Consumer Genetic  Testing
Sandra Soo-Jin Lee, Ph.D., Senior Research  Fellow, Center for Biomedical Ethics, Stanford University Medical  School


Next-Generation Genetic  Counseling
Ramji Srinivasan, CEO & Co-Founder,  Counsyl

TDTC(CC) – Consumers, Clinicians and  Counseling
Erica Ramos, MS, CGC, Clinical Genomics  Specialist, Certified Genetic Counselor, Translational and Consumer  Genomics, Illumina, Inc.

For  exhibit and sponsorship information, including sponsored  podium presentations <http://www.triconference.com/click-thru/127354/?email=avivalev-ari@alum.berkeley.edu> , please  contact:

Jon Stroup  (Companies A-K)
Manager, Business  Development
Cambridge Healthtech Institute
T: (+1)  781-972-5483
E: jstroup@healthtech.com

Joseph Vacca (Companies  L-Z)
Manager, Business Development
Cambridge Healthtech  Institute
T: (+1) 781-972-5431
E: jvacca@healthtech.com 

Cambridge Healthtech Institute’s Second Annual

Part of the 21st Annual Molecular Medicine Tri-Conference
February 13-14, 2014 | Westin St. Francis | San Francisco, CA

Cambridge Healthtech Institute’s Second Annual Genomics in Medicine symposium will provide insight into common implementation issues as they relate to practicing clinicians, as well as address the evolving role of genomics in guiding diagnoses and treatments. Special focus will be given to processing and delivering complex data to the practicing physician. Integration of decision-making tools with existing patient records will also be discussed. This symposium will provide a forum for those hoping to learn more about genomic medicine as well as those currently practicing and looking for an update on the field’s latest advances.

Thursday, February 13

7:30 am Registration and Morning Coffee


9:00 Chairperson’s Opening Remarks


Incidental Findings in Genomic Medicine: The Debate and the Data

Robert C. Green, M.D., MPH, Director, G2P Research Program; Associate Director, Research, Partners Center for Personalized Genetic Medicine, Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School

Genomics is being rapidly integrated into medicine with many unanswered questions about how and how much risk information should be communicated, and how such information will influence physician and patient behaviors, health outcomes and health care costs. This presentation will summarize data from over 10 years of experimental work in translational genomics and health outcomes, discuss recent ACMG recommendations for incidental findings and preview results from our newest NIH-funded studies, the ongoing MedSeq Project and the recently funded BabySeq Project.

9:35 Genomic Medicine Implementations for Primary Care

Erwin Bottinger, M.D., The Irene and Dr. Arthur Fishberg Professor of Medicine; Director, The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine, Mount Sinai

Increasingly, genomic discoveries provide opportunities to personalize medication use and prediction and prevention of common chronic diseases. However, effective integration of genomic medicine in busy primary care practices is hampered by multiple barriers, including provider education gaps and negative impact on clinical workflow. Innovative programs for real-time, point-of-care integration of genomic medicine for primary care providers through genome-informed clinical decision support enabled in electronic health records will be presented.

10:05 Ethical Issues Related to the Return of Incidental Findings in Children/Families

Ingrid A. Holm, M.D., MPH, Director, Phenotyping Core, Program in Genomics, Divisions of Genetics and Endocrinology, Boston Children’s Hospital

10:35 Coffee Break with Exhibit and Poster Viewing


11:05 Reducing the Complexity of Clinical Omics Reporting for Clinicians and Laboratories

Jonathan Hirsch, Founder & President, Syapse

Syapse has built a cloud-based software platform that enables the use of omics at the point of care through an interactive web portal. We will describe how clinical omics labs use the Syapse platform to maintain an evolving omics knowledgebase which drives updated clinical reporting through interactive, intuitive interfaces designed for ease of use and comprehension. We will describe how hospitals use the Syapse platform to place omics results in the context of clinical guidelines, enabling physicians to easily adopt and integrate omics into their clinical workflow.

11:35 Beyond Sequence: Integration of Full-Genome Technologies for Personalized Medicine in the Clinic

Raphael Lehrer, Founder and Chief Scientist, GeneKey

Here we describe how we have used a combination of multiple full genome technologies to triangulate on key dysregulated mechanisms in a patient’s sample. By using a combination of systems biology and statistical analysis, we are able to draw conclusions far more precise than one could from sequence alone. We describe how we have applied in the clinic with patients and their oncologists and what we have seen/learned to date, including cases where the dysfunction is not mutation-based.

Sponsored by


12:05 pm Targeted NGS of Clinical Samples: Overcoming the Challenges of Obtaining High Quality Data from Low Quality DNA

Diane Ilsley, Ph.D., Marketing Manager, Genomic Services, Asuragen

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:05 Session Break


1:50 Chairperson’s Remarks

1:55 Genome Sequencing in the Clinic: Found the Variants – Now What?

Jennifer Friedman, M.D., Associate Clinical Professor, Neurosciences and Pediatrics, UCSD/Rady Children’s Hospital San Diego

Advances in genome sequencing hold tremendous promise for providing answers and tailored therapies for undiagnosed patients. How to interpret, transmit and act upon volumes of complex data remains a challenge for sequencing providers, physicians and their patients. This presentation will use case-based examples to demonstrate promises and pitfalls encounter along the way.

2:25 The Answer is There but I Don’t Understand It: Solutions from the Front Line

Vanya Gant, Ph.D., FRCP, FRCPath, Divisional Clinical Director for Infection, The Department of Microbiology, UCLH NHS Foundation Trust

This talk will introduce the concept and fundamental problem of how to present complex NGS datasets to clinicians – and how this will be critical for rapid uptake. A case study outlining the principles behind a very new and innovative pathology project and way of delivering healthcare diagnostics will also be presented.

2:55 Refreshment Break with Exhibit and Poster Viewing

3:25 Using a Patient’s Genetic Information in the Real World

Michael F. Christman, Ph.D., President and CEO, Coriell Institute for Medical Research

When a patient needs a new prescription, it will be necessary for the physician to quickly and securely access his/her genetic data to understand drug efficacy prior to dosing. Who will patients and doctors trust to store and interpret the data? Coriell and the CPMC research study have defined several of the key barriers to accelerate the adoption and routine use of genomics in medicine and have proposed solutions that are generally applicable.

3:55 Developing Clinical Sequencing Assays at Einstein-Montefiore

Cristina Montagna, Ph.D., Associate Professor, Genetics, Albert Einstein College of Medicine

We developed a program to introduce Next-Generation Sequencing (NGS) to address the needs of individuals receiving clinical care at Montefiore Medical Center. After extensive dialogue with clinicians, we designed a custom gene panel, spanning 5Mb and consisting of 650 genes targeting known Mendelian loci, some pediatric diseases and several hotspot genes in various cancer types. By building a basic infrastructure for transitioning NSG in the clinic we have encountered roadblocks and established protocols to overcome these.

4:25 Breakout Discussions (see website for details)

5:25 Close of Day

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Third Annual TCGC: The Clinical Genome Conference, San Francisco, June 10-12, 2014 by Bio-IT World and Cambridge Healthtech Institute

Reporter: Aviva Lev-Ari, PhD, RN


UPDATED on 5/1/2014

Register by May 2 for

Hotel Kabuki, San Francisco, CA

June 10 – 12, 2014





Mining the Genome for Medicine Clinical Genome Conference.com


The unstoppable march of genomics into clinical practice continues. In an ideal world, the expanding use of genomic tools will identify disease before the onset of clinical symptoms and determine individualized drug treatment leading to precision medicine. However, many challenges remain or the successful translation of genomic knowledge and technologies into health advances and actionable patient care. Join vital discussions of the applications, questions and solutions surrounding clinical genome analysis.


Atul Butte, M.D., Ph.D.

Division Chief and Associate Professor, Stanford University School of Medicine; Director, Center for Pediatric Bioinformatics, Lucile Packard Children’s Hospital

David Galas, Ph.D.

Principal Scientist, Pacific Northwest Diabetes Research Institute

Gail P. Jarvik, M.D., Ph.D.

Head, Division of Medical Genetics, Arno G. Motulsky Endowed Chair in Medicine and Professor, Medicine and Genome Sciences, University of Washington Medical Center

John Pfeifer, M.D., Ph.D.

Vice Chair, Clinical Affairs, Pathology and Immunology; Professor, Pathology and Immunology, Washington University

John Quackenbush, Ph.D.

Professor, Dana-Farber Cancer Institute and Harvard School of Public Health; Co-Founder and CEO, GenoSpace

Topics Include:

• Working with the Payer Process

• Genome Variation and Clinical Utility

• NGS Is Guiding Therapies

• NGS Is Redefining Genomics

• Interpretation and Translation to the Client

• Integrating Genomic Data into the Clinic


Cambridge Healthtech Institute

250 First Avenue, Suite 300

Needham, MA 02494




7:30 am Conference Registration and Morning Coffee

Working with the Payer Process

8:30 Chairperson’s Opening Remarks


8:45 Case Study on Working through the Payer Process

John Pfeifer, M.D., Ph.D., Vice Chair, Clinical Affairs, Pathology; Professor,

Pathology and Immunology; Professor, Obstetrics and Gynecology, Washington

University School of Medicine

If next-generation sequencing (NGS) is to become a part of patient care in routine clinical practice (whether in the setting of oncology or in the setting of inherited genetic disorders), labs that perform clinical NGS must be reimbursed for the testing they provide. Genomics and Pathology Services at Washington University in St. Louis (GPS@WUSTL) will be used as a case study of a national reference lab that has been successful in achieving high levels of reimbursement for the clinical NGS testing it performs, including from private payers. The reasons for GPS’s success will be discussed, including NGS test design, clinical focus of testing, use of different models for reimbursement and payer education.

9:30 Implementation of Clinical Cancer Genomics within an Integrated

Healthcare System

Lincoln D. Nadauld, M.D., Ph.D., Director, Cancer Genomics, Intermountain Healthcare

Precision cancer medicine involves the detection of tumor-specific DNA alterations followed by treatment with therapeutics that specifically target the actionable mutations. Significant advances in genomic technologies have now rendered extended genomic analyses of human malignancies technologically and financially feasible for clinical adoption. Intermountain Healthcare, an integrated healthcare delivery system, is taking advantage of these advances to programmatically implement genomics into the regular treatment of cancer patients to improve clinical outcomes and reduce treatment costs.


Payer’s Dilemma: Evolution vs. Revolution

As falling genome sequencing costs help clinicians refine patient diagnoses and therapeutic approaches, new complexities arise over insurance coverage of such tests, classification by CPT codes and other reimbursement issues. Experts on this panel will discuss payer challenges and changes—both rapid and gradual—occurring alongside these advances in clinical genomics.

Moderator: Katherine Tynan, Ph.D., Business Development & Strategic Consulting for Diagnostics

Companies, Tynan Consulting LLC


Tonya Dowd, MPH, Director, Reimbursement Policy and Market Access, Quorum Consulting

Mike M. Moradian, Ph.D., Director of Operations and Molecular Genetics Scientist, Kaiser

Permanente Southern California Regional Genetics Laboratory

Rina Wolf, Vice President of Commercialization Strategies, Consulting and Industry Affairs, XIFIN

Additional Panelists to be Announced

10:45 Networking Coffee Break

11:15 Beyond Genomics: Preparing for the Avalanche of Post-Genomic

Clinical Findings

Jimmy Lin, M.D., Ph.D., President, Rare Genomics Institute

Whole genomic and exomics sequencing applied clinically is revealing newly discovered genes and syndromes at an astonishing rate. While clinical databases and variant annotation continue to grow, much of the effort needed is functional analysis and clinical correlation. At RGI, we are building a comprehensive functional genomics platform that includes electronic health records, biobanking, data management, scientific idea crowdsourcing and contract research sourcing.

11:45 The MMRF CoMMpass Clinical Trial: A Longitudinal Observational

Trial to Identify Genomic Predictors of Outcome in Multiple Myeloma

Jonathan J. Keats, Ph.D., Assistant Professor, Integrated Cancer Genomics Division, Translational

Genomics Research Institute

12:15 pm Luncheon Presentation: Sponsored by

Big Data & Little Data – From Patient Stratification

to Precision Medicine

Colin Williams, Ph.D., Director, Product Strategy, Thomson Reuters

Molecular data has the power, when unlocked, to transform our understanding of disease to support drug discovery and patient care. The key to unlocking this potential is ‘humanising’ the data, through tools and techniques, to a level that supports interpretation by Life Science professionals. This talk will focus on strategies for extracting insight from ‘big data’ by shrinking it to ‘little data’, with a focus on applications to support patient stratification in drug discovery and for practising precision medicine in a clinical setting.

Genome Variation and Clinical Utility

1:45 Chairperson’s Remarks


1:50 Lessons from the Clinical Sequencing Exploratory

Research (CSER) Consortium: Genomic Medicine


Gail P. Jarvik, M.D., Ph.D., Head, Division of Medical Genetics, Arno G. Motulsky Endowed Chair in Medicine and Professor, Medicine and Genome

Sciences, University of Washington Medical Center

Recent technologies have led to affordable genomic testing. However, implementation of genomic medicine faces many hurdles. The Clinical Sequencing Exploratory Research (CSER) Consortium, which includes nine genomic medicine projects, was formed to explore these challenges and opportunities. Dr. Jarvik is the PI of a CSER genomic medicine project and of the CSER coordinating center. She will focus on the frequency of exomic incidental findings, including those of the 56 genes recommended for incidental finding return by the ACMG. The CSER group has annotated the putatively pathogenic and novel variants of the Exome Variant Server (EVS) to estimate the rate of these in individuals of European and African ancestry. Experience with consenting and returning incidental findings will also be reviewed.

2:35 Decoding the Patient’s Genome: Clinical Use of Genome-Wide

Sequencing Data

Elizabeth Worthey, Ph.D., Assistant Professor, Pediatrics & Bioinformatics Program, Human & Molecular Genetics Center, Medical College of Wisconsin

Despite significant advances in our understanding of the genetic basis of disease, genomewide identification and subsequent interpretation of the molecular changes that lead to human disease represent the most significant challenges in modern human genetics.

Starting in 2009 at MCW, we have performed clinical WGS and WES to diagnose patients coming from across all clinical specialties. I will discuss findings, pros and cons in approach, challenges remaining and where we go next.

3:05 Analyzing Variants with a DTC Genetics Database

Brian Naughton, Ph.D., Founding Scientist, 23andMe, Inc.

Sequencing a genome results in dozens of potentially disease-causing variants (VUS). I describe some examples of using the 23andMe database, including quick recontact of participants, to determine if a variant is disease-causing.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing


Genome Interpretation Software Solutions: Software Spotlights

(Sponsorship Opportunities Available)

Obtaining clinical genome data is rapidly becoming a reality, but analyzing and interpreting the data remains a bottleneck. While there are many commercial software solutions and pipelines for managing raw genome sequence data, providing the medical interpretation and delivering a clinical diagnosis will be the critical step in fulfilling the promise of genomic medicine. This session will showcase how genome data analysis companies are streamlining the genomic diagnostic pipeline through:

• Transferring raw sequencing data

• Interpreting genetic variations

• Building new software and cloud-based analysis pipelines

• Investigating the genetic basis of disease or drug response

• Integrating with other clinical data systems

• Creating new medical-grade databases

• Reporting relevant clinical information in a physician-friendly manner

• Continuous learning feedback

4:15 Software Spotlight #1

4:30 Copy Number Variant Detection Using Sponsored by

Next-Generation Sequencing: State of the Art

Alexander Kaplun, Ph.D., Field Applications Scientist, BIOBASE

This talk will provide a short review about the current state of the art in detection of larger variants that have an important role in many diseases such as haplotypes, indels, repeats, copy number variants (CNVs), structural variants (SVs) and fusion genes using NGS methods, and an outlook to their use for pharmacogenomic genotyping.

4:45 Software Spotlight #3

5:00 Software Spotlight #4

5:15 Software Spotlight #5

5:30 Pertinence Metric Enables Hypothesis-Independent Sponsored by

Genome-Phenome Analysis in Seconds

Michael M. Segal, M.D., Ph.D., Chief Scientist, SimulConsult

Genome-phenome analysis combines processing of a genomic variant table and comparison of the patient’s findings to those of known diseases (“phenome”). In a study of 20 trios, accuracy was 100% when using trios with family-aware calling, and close to that if only probands were used. The gene pertinence metric calculated in the analysis was 99.9% for the causal genes. The analysis took seconds and was hypothesis-independent as to form of inheritance or number of causal genes. Similar benefits were found in gene discovery situations.

6:00 Welcome Reception in the Exhibit Hall with Poster Viewing

7:00 Close of Day


7:30 am Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee

NGS Is Guiding Therapies

8:30 Chairperson’s Opening Remarks

8:35 Next-Generation Sequencing Approaches for Identifying Patients

Who May Benefit from PARP Inhibitor Therapy

Mitch Raponi, Ph.D., Senior Director and Head, Molecular Diagnostics, Clovis Oncology

The following questions will be addressed: What biomarkers should we be focusing on to identify appropriate patients who will likely benefit from PARP inhibitors? How can we apply next-generation sequencing technologies to identify all patients who will respond to the PARP inhibitor rucaparib? What regulatory challenges are we faced with for approval of NGS companion diagnostics?

9:05 Whole-Genome and Whole-Transcriptome Sequencing to Guide

Therapy for Patients with Advanced Cancer

Glen J. Weiss, M.D., MBA, Director, Clinical Research, Cancer Treatment Centers of America

Treating advanced cancer with agents that target a single-cell surface receptor, up-regulated or amplified gene product or mutated gene has met with some success; however, eventually the cancer progresses. We used next-generation sequencing technologies (NGS) including whole-genome sequencing (WGS), and where feasible, whole-transcriptome sequencing (WTS) to identify genomic events and associated expression changes in advanced cancer patients. While the initial effort was a slower process than anticipated due to a variety of issues, we demonstrated the feasibility of using NGS in advanced cancer patients so that treatments for patients with progressing tumors may be improved. This lecture will highlight some of these challenges and where we are today in bringing NGS to patients.

9:35 The SmartChip TE™ Target Enrichment System for Sponsored by

Clinical Next-Gen Sequencing

Gianluca Roma, MS MBA, Director, Product Management, WaferGen Biosystems

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

Data Mining


10:45 Translating a Trillion Points of Data into

Therapies, Diagnostics and New Insights into Disease

Atul Butte, M.D., Ph.D., Division Chief and Associate Professor, Stanford University School of Medicine; Director, Center for Pediatric Bioinformatics,

Lucile Packard Children’s Hospital; Co-Founder, Personalis and Numedii

There is an urgent need to translate genome-era discoveries into clinical utility, but the difficulties in making bench-to-bedside translations have been well described. The nascent field of translational bioinformatics may help. Dr. Butte’s lab at Stanford builds and applies tools that convert more than a trillion points of molecular, clinical and epidemiological data— measured by researchers and clinicians over the past decade—into diagnostics, therapeutics and new insights into disease. Dr. Butte, a bioinformatician and pediatric endocrinologist, will highlight his lab’s work on using publicly available molecular measurements to find new uses for drugs, including drug repositioning for inflammatory bowel disease, discovering new treatable inflammatory mechanisms of disease in type 2 diabetes and the evaluation of patients presenting with whole genomes sequenced.

11:30 DGIdb – Mining the Druggable Genome

Malachi Griffith, Ph.D., Research Faculty, Genetics, The Genome Institute, Washington University School of Medicine

In the era of high-throughput genomics, investigators are frequently presented with lists of mutated or otherwise altered genes implicated in human disease. Numerous resources exist to generate hypotheses about how such genomic events might be targeted therapeutically or prioritized for drug development. The Drug-Gene Interaction database (DGIdb) mines these resources and provides an interface for searching lists of genes against a compendium of drug-gene interactions and potentially druggable genes. DGIdb can be accessed at dgidb.org.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Luncheon Presentation (Sponsorship Opportunity Available)


The unstoppable march of genomics into clinical practice continues. In an ideal world, the expanding use of genomic tools will identify disease before the onset of clinical symptoms and determine individualized drug treatment leading to precision medicine. However, many challenges remain for the successful translation of genomic knowledge and technologies into health advances and clinical practice.

Bio-IT World and Cambridge Healthtech Institute are again proud to host the Third Annual TCGC: The Clinical Genome Conference, inviting stakeholders from all arenas impacting clinical genomics to share new findings and solutions for advancing the application of clinical genome medicine.

TCGC brings together many constituencies for frank and vital discussion of the applications, questions and solutions surrounding clinical genome analysis, including scientists, physicians, diagnosticians, genetic counselors, bioinformaticists, ethicists, regulators, insurers, lawyers and administrators.

Topics addressing successful translation of genomic knowledge and technologies into advancement of clinical utility (medicines and diagnostics) include but are not limited to:

Scientific Investigation and Interpretation

  • Technologies/Platforms
  • WGS/Exome/Single-Cell Sequencing
  • Drug and Diagnostic Targets
  • Interpretation and Analysis Pipelines
  • Case Studies

Clinical Integration and Implementation

  • Mechanisms to Monitor Genomic Medicine
  • Determining Clinical Utility
  • Standardization/Regulation/Certification
  • Reimbursement
  • Data Management
  • Diagnostic Lab Infrastructure
  • HIT/Data Integration
  • Reporting Results to Patients/Physicians

Call for Speakers
For a limited time, we are inviting researchers and clinicians applying genome analysis tools in clinical settings, as well as regulators and administrators implementing genomics into the clinic, to submit proposals for platform presentations. Please note that due to limited speaking slots, preference is given to abstracts from those within pharmaceutical and biopharmaceutical companies, regulators and those from academic centers. Additionally, as per CHI policy, a select number of vendors/consultants who provide products and services to these genomic researchers are offered opportunities for podium presentation slots based on a variety of Corporate Sponsorships.

All proposals are subject to review by the organizers and Scientific Advisory Committee.

Please click here to submit a proposal.

Submission deadline for priority consideration: November 15, 2013

For more details on the conference, please contact:
Mary Ann Brown
Executive Director, Conferences
Cambridge Healthtech Institute
250 First Avenue, Suite 300
Needham, MA 02494
T:  781-972-5497
E:  mabrown@healthtech.com

For exhibit and sponsorship opportunities, please contact:
Jay Mulhern
Manager, Business Development, Conferences & Media
Cambridge Healthtech Institute
250 First Avenue, Suite 300
Needham, MA 02494
T: 781-972-1359
E: jmulhern@healthtech.com




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Genome Sequencing of the Healthy

Curators: Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN


Key Issues in Genome Sequencing of Healthy Individuals
Eric Topol, MD, Genomic Medicine

I briefly review 3 important articles that recently appeared, each touching on important controversies in the use of whole genome sequencing


I briefly review 3 important articles that recently appeared, each touching on important controversies in the use of whole genome sequencing:
1. Should Healthy People Have Their Genomes Sequenced At This Time? Wall Street Journal, February 15, 2013.
2. A Genetic Code for Genius? Wall Street Journal, February 15, 2013.
3. Francke U, Djamco C, Kiefer AK, et al. Dealing with the unexpected: consumer responses to direct-access BRCA mutation testing. PeerJ. 2012;1:e8. DOI 10.7717/peerj.8
Welcome to another segment on genomic medicine. Today, I want to get into 3 different articles: 2 from the Wall Street (“Medical”) Journal and the other from a new open access journal, PeerJ. All of them are related to the issues of genome sequencing.
First, there was a debate about whether all healthy people should have their genomes sequenced. It was a debate between Atul Butte from Stanford and Robert Green from Harvard. In this debate, they made a number of really good points, and I have linked you to that article if you’re interested.
Basically, is it too early to get sequencing because we need millions of people to have whole genome sequencing who are healthy in order for that information to be truly informative. The price continues to drop. So even though the sequencing that is done today would still be valid if it’s done accurately, the problem we have, of course, is a lack of enough people who are phenotyped with a particular condition to extract all the best information that is truly informative from whole genome sequencing.
 it’s unlikely that even 2000 individuals with high IQ will be particularly informative but also, of course, what this could do from a bioethical standpoint. I’ll leave that to your imagination and thoughts as to where this could go – that is, trying to understand, even with limited power, the genomics of intelligence.
The third article, which is also very interesting, comes from this new journal called PeerJ. I’m on the editorial board of that journal, and I think it’s terrific to see open access, high-quality biomedical articles.
This one comes from the company 23andMe. From a very large number of individuals – now over 200,000 and rapidly approaching 1 million – who have had genome scans, a large number of women had information about the BRCA gene and whether they had a significant mutation. From these women who volunteered to participate in this study, we learned that they had no serious psychological repercussions from knowledge of this highly actionable BRCA pathogenic mutation.
This goes along with the previous study that we had done at Scripps led by my colleague Cinnamon Bloss in the New England Journal of Medicine, where, in thousands of individuals who had genome scans and had such data as ApoE4 status known to them for the first time, there were no significant negative psychological repercussions.

Should Healthy People Have Their Genomes Sequenced At This Time?

‘Patients in Waiting’

Injecting so much uncertain genetic information into the doctor-patient relationship could create legions of “patients in waiting” leading to unnecessary tests, harmful outcomes and lifelong anxiety. As private software companies compete to provide more genomic “findings” to a medical culture that is trained to search for diagnostic fire when they smell the smoke of disease risk, there are potential benefits. But there is also a real possibility that medical resources will be squandered and patients could be harmed.

Perhaps we all underestimated how complicated it would be to move genomic knowledge into the practice of medicine and public health. Now is the time to make sure we get this right through rigorous basic and clinical studies that define which mutations are dangerous, and distinguish useful from unnecessary interventions. Soon, genomic insights will give us early warnings about life-threatening illnesses that we may be able to prevent. Soon, standards will be available to guide doctors about which findings are meaningful and which are not.

Soon, there may be evidence to support the benefits of screening healthy individuals. But not today.

Table 1. Performance values for genome sequenc...

Table 1. Performance values for genome sequencing technologies including Sanger methods and Massively Parallel Seqeuncing methods. Sinville, R. and Soper, S. A. High resolution DNA separations using microchip electrophoresis. J. Sep. Sci. 2007, 30, 1714 – 1728 Morozova,O. and Marra, M. A. Applications of next-generation sequencing technologies in functional genomics. Genomics. 92 (2008) 255–264 (Photo credit: Wikipedia)


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