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Posts Tagged ‘Full genome sequencing’


9:20AM 11/12/2014 – 10th Annual Personalized Medicine Conference at the Harvard Medical School, Boston

REAL TIME Coverage of this Conference by Dr. Aviva Lev-Ari, PhD, RN – Director and Founder of LEADERS in PHARMACEUTICAL BUSINESS INTELLIGENCE, Boston http://pharmaceuticalintelligence.com

9:20 a.m. Panel Discussion – Genomic Technologies

Genomic Technologies

The greatest impetus for personalized medicine is the initial sequencing of the human genome at the beginning of this Century. As we began to recognize the importance of genetic factors in human health and disease, efforts to understand genetic variation and its impact on health have accelerated. It was estimated that it cost more than two billion dollars to sequence the first human genome and reduction in the cost of sequence became an imperative to apply this technology to many facets of risk assessment, diagnosis, prognosis and therapeutic intervention. This panel will take a brief historical look back at how the technologies have evolved over the last 15 years and what the future holds and how these technologies are being applied to patient care.

Genomic Technologies

Opening Speaker and Moderator:

George Church, Ph.D.
Professor of Genetics, Harvard Medical School; Director, Personal Genomics

Genomic Technologies and Sequencing

  • highly predictive, preventative
  • non predictive

Shareable Human Genomes Omics Standards

$800 Human Genome Sequence – Moore’s Law does not account for the rapid decrease in cost of Genome Sequencing

Genome Technologies and Applications

  • Genia nanopore – battery operated device
  • RNA & protein traffic
  • Molecular Stratification Methods – more than one read, sequence ties
  • Brain Atlas  – transcriptome of mouse brains
  • Multigenics – 700 genes: hGH therapies

Therapies

  • vaccine
  • hygiene
  • age

~1970 Gene Therapy in Clinical Trials

Is Omic technologies — a Commodity?

  • Some practices will have protocols
  • other will never become a commodity

 

Panelists:

Sam Hanash, M.D., Ph.D. @MDAndersonNews

Director, Red & Charline McCombs Institute for Early Detection & Treatment of Cancer MD Anderson Cancer Center

Heterogeneity among Cancer cells. Data analysis and interpretation is very difficult, back up technology

Proteins and Peptides before analysis with spectrometry:

  • PM  – Immunotherapy approaches need be combined with other techniques
  • How modification in protein type affects disease
  • amplification of an aberrant protein – when that happens cancer developed. Modeling on a CHip of peptide synthesizer

Mark Stevenson @servingscience

Executive Vice President and President, Life Sciences Solutions
Thermo Fisher Scientific

Issues of a Diagnostics Developer:

  • FDA regulation, need to test on several tissues
  • computational environment
  • PCR, qPCR – cost effective
  • BGI – competitiveness

Robert Green, MD @BrighamWomens

Partners, Health Care Personalized Medicine — >>Disclosure: Illumina and three Pharmas

Innovative Clinical Trial: Alzheimer’s Disease, integration of sequencing with drug development

  • Population based screening with diagnosis
  • Cancer predisposition: Cost, Value, BRCA
  • epigenomics technologies to be integrated
  • Real-time diagnostics
  • Screening makes assumption on Predisposition
  • Public Health view: Phenotypes in the Framingham Studies: 64% pathogenic genes were prevalent – complication based in sequencing.

Questions from the Podium:

  • Variants analysis
  • Metastasis different than solid tumor itself – Genomics will not answer issues related to tumor in special tissues variability

 

 

 

 

– See more at: http://personalizedmedicine.partners.org/Education/Personalized-Medicine-Conference/Program.aspx#sthash.qGbGZXXf.dpuf

@HarvardPMConf

#PMConf

@SachsAssociates

 

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Reporter: Aviva Lev-Ari, PhD, RN

 

Researchers Report on Mutational Patterns in Adenoid Cystic Carcinoma

May 20, 2013

NEW YORK (GenomeWeb News) – A Memorial Sloan-Kettering Cancer Center-led team has taken an exome- and genome-sequencing centered look at the mutations that may be found in the salivary gland cancer adenoid cystic carcinoma, or ACC.

As they reported in Nature Genetics online yesterday, the researchers did exome or genome sequencing on five-dozen matched ACC tumor and normal pairs.

Their analysis unearthed relatively few glitches in each tumor’s protein-coding sequences. But the group found suspicious mutations to several main pathways, including some — such as the PI3-kinase, fibroblast growth factor, and insulin-like growth factor-containing pathway — that may make promising treatment targets.

“Our discovery of genomic alterations in targetable pathways suggests potential avenues for novel treatments to address a typically chemoresistant malignancy,” corresponding author Timothy Chan, an oncology researcher at Memorial Sloan-Kettering, and his colleagues wrote, noting that “[v]erified ACC cell lines are needed to further substantiate the clinical usefulness of the mutations identified here.”

A few genetic glitches have been linked to ACC in the past, the team noted, including a fusion between the transcription factor genes MYB and NFIB. The tumors are also notorious for having higher-than-usual expression of certain genes, such as the epidermal growth factors. Even so, there is still a ways to go in characterizing and treating the aggressive cancer.

To get a better sense of the nature and frequency of mutations involved in ACC, the researchers used Illumina’s HiSeq2000 to do exome sequencing on 55 matched ACC and normal samples, as well as whole-genome sequencing on five more tumor-normal pairs.

For the exome sequencing experiments, they used Agilent SureSelect kits to capture protein-coding portions of the genome prior to sequencing. In the subsequent analyses, meanwhile, the group relied on Life Tehnologies’ SOLiD and Illumina’s MiSeq platforms to verify apparent single nucleotide glitches and small insertions and deletions.

With 106-fold coverage of the exomes, on average, and 37-fold average coverage of the genomes, the group was able to track down a mean of almost two-dozen somatic coding alterations per tumor.

When they used an algorithm called CHASM to distinguish between driver and passenger mutations in a set of 710 validated non-synonymous mutations, the researchers saw an over-representation of apparent driver mutations affecting genes known for processes ranging from chromatin regulation and DNA damage response to signaling and metabolism.

For instance, more than one-third of the tumors harbored mutations to chromatin regulators or chromatin state modifying genes such as SMARCA2, CREBBP, and KDM6A. Similarly, the researchers tracked down multiple mutations to genes coding for enzymes involved in adding or removing methylation and acetylation marks to histones.

Glitches to DNA damage response pathways also turned up in multiple tumors, they reported, as did mutations involving genes from the FGF-IGF-PI3K and other signaling pathways.

Some 57 percent of the tumors tested contained the MYB-NFIB fusion that had been implicated in ACC previously. But the new analysis also turned up mutations affecting genes that interact with MYB and in the NFIB gene itself, pointing to widespread — and perhaps complex — involvement for the two transcription factors in ACC.

“Our data highlight MYB as an active oncogenic partner in fusion transcripts in ACC,” the study’s authors said, “but also suggest a separate role for NFIB, given the presence of mutations specific to this gene.”

Going forward, the group hopes to see further analyses on alterations uncovered in the current study, particularly those falling in pathways that might be prone to clinical interventions.

“[O]ur data provide insights into the genetic framework underlying ACC oncogenesis,” the researchers concluded, “and establish a foundation for identifying new therapeutic strategies.”

 

 

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Finding the Genetic Links in Common Disease:  Caveats of Whole Genome Sequencing Studies

Writer and Reporter: Stephen J. Williams, Ph.D.

In the November 23, 2012 issue of Science, Jocelyn Kaiser reports (Genetic Influences On Disease Remain Hidden in News and Analysis)[1] on the difficulties that many genomic studies are encountering correlating genetic variants to high risk of type 2 diabetes and heart disease.  At the recent American Society of Human Genetics annual 2012 meeting, results of several DNA sequencing studies reported difficulties in finding genetic variants and links to high risk type 2 diabetes and heart disease.  These studies were a part of an international effort to determine the multiple genetic events contributing to complex, common diseases like diabetes.  Unlike Mendelian inherited diseases (like ataxia telangiectasia) which are characterized by defects mainly in one gene, finding genetic links to more complex diseases may pose a problem as outlined in the article:

  • Variants may be so rare that massive number of patient’s genome would need to be analyzed
  • For most diseases, individual SNPs (single nucleotide polymorphisms) raise risk modestly
  • Hard to find isolated families (hemophilia) or isolated populations (Ashkenazi Jew)
  • Disease-influencing genes have not been weeded out by natural selection after human population explosion (~5000 years ago) resulted in numerous gene variants
  • What percentage variants account for disease heritability (studies have shown this is as low as 26% for diabetes with the remaining risk determined by environment)

Although many genome-wide-associations studies have found SNPs that have causality to increasing risk diseases such as cancer, diabetes, and heart disease, most individual SNPs for common diseases raise risk by about only 20-40% and would be useless for predicting an individual’s chance they will develop disease and be a candidate for a personalized therapy approach.  Therefore, for common diseases, investigators are relying on direct exome sequencing and whole-genome sequencing to detect these medium-rare risk variants, rather than relying on genome-wide association studies (which are usually fine for detecting the higher frequency variants associated with common diseases).

Three of the many projects (one for heart risk and two for diabetes risk) are highlighted in the article:

1.  National Heart, Lung and Blood Institute Exome Sequencing Project (ESP)[2]: heart, lung, blood

  • Sequenced 6,700 exomes of European or African descent
  • Majority of variants linked to disease too rare (as low as one variant)
  • Groups of variants in the same gene confirmed link between APOC3 and higher risk for early-onset heart attack
  • No other significant gene variants linked with heart disease

2.  T2D-GENES Consortium: diabetes

Sequenced 5,300 exomes of type 2 diabetes patients and controls from five ancestry groups
SNP in PAX4 gene associated with disease in East Asians
No low-frequency variant with large effect though

3.  GoT2D: diabetes

  • After sequencing 2700 patient’s exomes and whole genome no new rare variants above 1.5% frequency with a strong effect on diabetes risk

A nice article by Dr. Sowmiya Moorthie entitled Involvement of rare variants in common disease can be found at the PGH Foundation site http://www.phgfoundation.org/news/5164/ further discusses this conundrum,  and is summarized below:

“Although GWAs have identified many SNPs associated with common disease, they have as yet had little success in identifying the causative genetic variants. Those that have been identified have only a weak effect on disease risk, and therefore only explain a small proportion of the heritable, genetic component of susceptibility to that disease. This has led to the common disease-common variant hypothesis, which predicts that common disease-causing genetic variants exist in all human populations, but each individual variant will necessarily only have a small effect on disease susceptibility (i.e. a low associated relative risk).

An alternative hypothesis is the common disease, many rare variants hypothesis, which postulates that disease is caused by multiple strong-effect variants, each of which is only found in a few individuals. Dickson et al. in a paper in PLoS Biology postulate that these rare variants can be indirectly associated with common variants; they call these synthetic associations and demonstrate how further investigation could help explain findings from GWA studies [Dickson et al. (2010) PLoS Biol. 8(1):e1000294][3].  In simulation experiments, 30% of synthetic associations were caused by the presence of rare causative variants and furthermore, the strength of the association with common variants also increased if the number of rare causative variants increased. “

one_of_many rare variants

Figure from Dr. Moorthie’s article showing the problem of “finding one in many”.

(please   click to enlarge)

Indeed, other examples of such issues concerning gene variant association studies occur with other common diseases such as neurologic diseases and obesity, where it has been difficult to clearly and definitively associate any variant with prediction of risk.

For example, Nuytemans et. al.[4] used exome sequencing to find variants in the vascular protein sorting 3J (VPS35) and eukaryotic transcription initiation factor 4  gamma1 (EIF4G1) genes, tow genes causally linked to Parkinson’s Disease (PD).  Although they identified novel VPS35 variants none of these variants could be correlated to higher risk of PD.   One EIF4G1 variant seemed to be a strong Parkinson’s Disease risk factor however there was “no evidence for an overall contribution of genetic variability in VPS35 or EIF4G1 to PD development”.

These negative results may have relevance as companies such as 23andme (www.23andme.com) claim to be able to test for Parkinson’s predisposition.  To see a description of the LLRK2 mutational analysis which they use to determine risk for the disease please see the following link: https://www.23andme.com/health/Parkinsons-Disease/. This company and other like it have been subjects of posts on this site (Personalized Medicine: Clinical Aspiration of Microarrays)

However there seems to be more luck with strategies focused on analyzing intronic sequence rather than exome sequence. Jocelyn Kaiser’s Science article notes this in a brief interview with Harry Dietz of Johns Hopkins University where he suspects that “much of the missing heritability lies in gene-gene interactions”.  Oliver Harismendy and Kelly Frazer and colleagues’ recent publication in Genome Biology  http://genomebiology.com/content/11/11/R118 support this notion[5].  The authors used targeted resequencing of two endocannabinoid metabolic enzyme genes (fatty-acid-amide hydrolase (FAAH) and monoglyceride lipase (MGLL) in 147 normal weight and 142 extremely obese patients.

These patients were enrolled in the CRESCENDO trial and patients analyzed were of European descent. However, instead of just exome sequencing, the group resequenced exome AND intronic sequence, especially focusing on promoter regions.   They identified 1,448 single nucleotide variants but using a statistical filter (called RareCover which is referred to as a collapsing method) they found 4 variants in the promoters and intronic areas of the FAAH and MGLL genes which correlated to body mass index.  It should be noted that anandamide, a substrate for FAAH, is elevated in obese patients. The authors did note some issues though mentioning that “some other loci, more weakly or inconsistently associated in the original GWASs, were not replicated in our samples, which is not too surprising given the sample size of our cohort is inadequate to replicate modest associations”.

PLEASE WATCH VIDEO on the National Heart, Lung and Blood Institute Exome Sequencing Project

https://www.youtube.com/watch?v=-Qr5ahk1HEI

REFERENCES

http://www.phgfoundation.org/news/5164/  PHG Foundation

1.            Kaiser J: Human genetics. Genetic influences on disease remain hidden. Science 2012, 338(6110):1016-1017.

2.            Tennessen JA, Bigham AW, O’Connor TD, Fu W, Kenny EE, Gravel S, McGee S, Do R, Liu X, Jun G et al: Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science 2012, 337(6090):64-69.

3.            Dickson SP, Wang K, Krantz I, Hakonarson H, Goldstein DB: Rare variants create synthetic genome-wide associations. PLoS biology 2010, 8(1):e1000294.

4.            Nuytemans K, Bademci G, Inchausti V, Dressen A, Kinnamon DD, Mehta A, Wang L, Zuchner S, Beecham GW, Martin ER et al: Whole exome sequencing of rare variants in EIF4G1 and VPS35 in Parkinson disease. Neurology 2013, 80(11):982-989.

5.            Harismendy O, Bansal V, Bhatia G, Nakano M, Scott M, Wang X, Dib C, Turlotte E, Sipe JC, Murray SS et al: Population sequencing of two endocannabinoid metabolic genes identifies rare and common regulatory variants associated with extreme obesity and metabolite level. Genome biology 2010, 11(11):R118.

Other posts on this site related to Genomics include:

Cancer Biology and Genomics for Disease Diagnosis

Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk

Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

Genomics-based cure for diabetes on-the-way

Personalized Medicine: Clinical Aspiration of Microarrays

Late Onset of Alzheimer’s Disease and One-carbon Metabolism

Genetics of Disease: More Complex is How to Creating New Drugs

Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

Centers of Excellence in Genomic Sciences (CEGS): NHGRI to Fund New CEGS on the Brain: Mental Disorders and the Nervous System

Cancer Genomic Precision Therapy: Digitized Tumor’s Genome (WGSA) Compared with Genome-native Germ Line: Flash-frozen specimen and Formalin-fixed paraffin-embedded Specimen Needed

Mitochondrial Metabolism and Cardiac Function

Pancreatic Cancer: Genetics, Genomics and Immunotherapy

Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Quantum Biology And Computational Medicine

Personalized Cardiovascular Genetic Medicine at Partners HealthCare and Harvard Medical School

Centers of Excellence in Genomic Sciences (CEGS): NHGRI to Fund New CEGS on the Brain: Mental Disorders and the Nervous System

LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2

Consumer Market for Personal DNA Sequencing: Part 4

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research: Part 3

Whole-Genome Sequencing Data will be Stored in Coriell’s Spin off For-Profit Entity

 

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Malaria Genomes

 

Curator: Larry H Bernstein, MD, FCAP

 

 Five Malaria Genomes Sequenced

Zimmerman et al.
Whole Genome Sequencing of Field Isolates Provides Robust Characterization of Genetic Diversity in Plasmodium vivax.
Scientists have sequenced the entire genomes of five Plasmodium vivax strains taken from the blood of patients on different continents, providing
  • a wealth of new data to help in the future mapping of malarial parasite traits such as
  • drug resistance, and
determine how different strains are geographically distributed.
  • identified over 80,000 SNPs that can form the basis of association studies and
  • population surveys to study the diversity of P. vivax in a single region.
Malaria.

Malaria. (Photo credit: maestro garabito/escuela potosina)

Malaria distribution map. Most countries with ...

Malaria distribution map. Most countries with a high distribution of malaria also have a high distribution of parasitic worm infections. (Photo credit: Wikipedia)

English: This thin film Giemsa stained microgr...

English: This thin film Giemsa stained micrograph reveals a mature Plasmodium vivax trophozoite. P. vivax trophozoites show amoeboid cytoplasm, large chromatin dots, and fine, yellowish-brown pigment. RBCs are enlarged 1 1/2 – 2X, and may be distorted. If visible, Schüffner’s dots may appear finer than those seen in P. vivax. (Photo credit: Wikipedia)

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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
http://www.linkedin.com/…/Key-Issues-in-Genome-Sequencing-218

http://boards.medscape.com/.2a38676f!comment=1

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.

SOURCE:
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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Reporter: Aviva Lev-Ari, PhD, RN

Inaugural Genomics in Medicine

Individualized Care for Improved Outcomes

February 11-12

Moscone North Convention Center • San Francisco, CA

Organized by

Cambridge Healthtech Institute

Monday, February 11

7:30 am Registration and Morning Coffee

8:25 Chairperson’s Opening Remarks

Screening for Rare and

Difficult to Diagnose Diseases

8:30 KEYNOTE PRESENTATION:

Genomically-Supported Diagnostic and

Drug Reposition Strategies out

of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center for Applied

Genomics, Children’s Hospital of Philadelphia

This talk will discuss genomic strategies applied in academia

to identify subsets of patients who, based on their genetic

make-up, are predicted to have a favorable response profile to

drugs that come from reposition opportunities.

9:00 Evolving Approaches to Mutation Detection in

Rare Diseases

Tom Scholl, Vice President, Research & Development,

Integrated Genetics, LabCorp

Emerging trends in this field that include the expansion of

content in clinical tests to include many loci and increased

clinical sensitivity by expanding numbers of mutations detected

or whole gene sequencing will be presented.

9:30 From Raw Sequencing Data to

Functional Interpretation

Daniel MacArthur, Ph.D., Group Leader, Analytic and

Translational Genetics Unit, Massachusetts General Hospital

This presentation will discuss the key lessons learned

from large-scale sequencing studies in both common and

rare diseases with a particular focus on finding mutations

underlying severe muscle diseases.

10:00 Coffee Break with Exhibit and Poster Viewing

10:30 Providing Whole Genome Sequencing in the Clinic

David Dimmock, M.D., Assistant Professor, Pediatrics,

Medical College of Wisconsin

This presentation will focus on advances in the implementation

of genome wide sequencing in clinical practice. It will address

counseling and consent issues specific to testing children.

Specifically, it will highlight the challenges of execution in the

acute care setting.

11:00 Clinical Utility of Whole Exome Sequencing

Christine M. Eng, M.D., Professor, Department of Molecular

and Human Genetics, Baylor College of Medicine

This presentation will discuss the role of whole exome

sequencing in the diagnostic evaluation of patients with

challenging phenotypes of genetic etiology. Examples of

clinical utility, directed medical care, and cost-effectiveness

of the whole exome approach to clinical diagnostics will be

presented.

11:30 A Neuronal Carnitine Deficiency Hypothesis

for Autism

Arthur L. Beaudet, M.D., Henry and Emma Meyer Professor

and Chair, Department of Molecular and Human Genetics,

Baylor College of Medicine

We have published a paper entitled “A common X-linked

inborn error of carnitine biosynthesis may be a risk factor for

nondysmorphic autism” (PMID: 22566635). We propose a

neuronal carnitine deficiency hypothesis as one risk factor

or cause for autism whereby 10-20% of autism might

be preventable.

12:00 pm Luncheon Presentation

(Sponsorship Opportunity Available) or Lunch on

Your Own

Predictive Tests for

Improved Patient Outcomes

1:25 Chairperson’s Remarks

1:30 Implementation of Personalized Healthcare into

Clinical Practice: Lessons Learned

Kathryn Teng, M.D., FACP, Director, Center for Personalized

Healthcare, Cleveland Clinic

Integrating a pharmacogenetics program into clinical practice

requires a vision for the future of healthcare and a roadmap to

reach that vision. Pioneering the road to achieving this vision

has brought challenges and has allowed for the creation of

solutions that might be applied universally.

2:00 Molecular Profiling of Tumors to Select Therapy

in Patients with Advanced Refractory Tumors

Ramesh Ramanathan, M.D., Medical Director, The Virginia

G. Piper Cancer Center Clinical Trials

This presentation will discuss molecular profiling of tumors

using IHC, CGH and whole genome/exome sequencing of

tumors to find actionable targets for therapy. Clinical trials

and case reports of patients treated by this approach will

be presented.

2:30 Sponsored Presentations (Opportunities Available)

3:00 Refreshment Break with Exhibit and

Poster Viewing

3:30 Gene Panels vs. Whole Exome Sequencing in

Cancer Molecular Testing

Madhuri Hegde, Ph.D., FACMG, Associate Professor, Senior

Director, Emory Genetics Laboratory, Department of Human

Genetics, Emory University School of Medicine

TriConference.com 5

Individualized Care for Improved Outcomes

4:00 Next Generation Sequencing and

Cancer Diagnostics

Phil Stephens, Ph.D., Vice President, Cancer Genomics,

Foundation Medicine

Foundation Medicine has developed FoundationOne™, a

CLIA-certified, comprehensive cancer genomic test that

analyzes routine clinical specimens for somatic alterations in

189 relevant cancer genes. Experience with the initial 1,000

consecutive patients will be presented.

4:30 KEYNOTE PRESENTATION:

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

The challenges and opportunities of implementing a broad

genotyping assay in routine clinical management of cancer

patients will be discussed. Snapshot was launched over 3

years ago at the Massachusetts General Hospital, with the

goal of providing all cancer patients with a genetic fingerprint

to guide therapeutic decisions. Lessons learned will be

outlined, and a roadmap to effectively move testing forward

into the Next Gen sequencing era.

5:00 Breakout Discussions (See Web for Details)

6:00 Close of Day

Tuesday, February 12

8:00 am Morning Coffee

Data Management and Analysis

8:10 Chairperson’s Remarks

8:15 Under the Hood of the 1000 Genomes Project

Mark A. DePristo, Ph.D., Associate Director, Medical

and Population Genetics Analysis, Broad Institute of MIT

and Harvard (on behalf of The 1000 Genomes Project

Consortium)

This presentation discusses the evolution of the nextgeneration

sequencing (NGS) data underlying the public

1000 Genomes Project resource, from some of the earliest

technologies of 2009 to today’s state-of-the-art data. It

will also highlight key NGS analytic advances originating

from the Project.

8:45 Delivering Genomic Medicine: Challenges

and Opportunities

Heidi L. Rehm, Ph.D., FACMG, Assistant Professor,

Pathology, BWH and Harvard Medical School; Director,

Laboratory for Molecular Medicine, Partners Healthcare

Center for Personalized Genetic Medicine

This talk will cover the speaker’s experience in offering clinical

sequencing to patients, from disease-targeted panels to whole

genome analyses as well as supporting the interpretation

and delivery of those results to physicians. It will also cover

approaches to data sharing within the community.

9:15 From Sequence Files to

Sponsored by

Physicians Report and the Tools

Needed to Get There

Martin Seifert, Ph.D., CEO,

Genomatix Software

Providing actionable biology from NGS data in a report useful

to the practicing clinician is difficult. Ensuring the report is

accurate, reproducible, and reflects the biology of the patient

is an even larger task. We will show examples of Genomatix’

approach to these issues and how we successfully ensure a

secure, accurate, and reproducible report, bridging the gap

from sequencer to clinician.

9:30 Rapid Identification of

Sponsored by

Disease Causative Mutations

Ali Torkamani, Ph.D., Co-Founder & CSO,

Cypher Genomics

Recent successes in clinical genome sequencing have

highlighted the potential for sequencing to greatly improve

molecular diagnosis and clinical decision-making. However,

these successes have relied upon large bioinformatics teams

and in-depth literature surveys. We will demonstrate how the

Cypher Genomics software service can quickly return a small

set of well-annotated genetic variants most likely to contribute

to a patient’s disease.

10:00 Coffee Break with Exhibit and

Poster Viewing

Getting Genomic Testing to Clinic

10:30 Sequence Data on Demand: Access,

Visualization and Communication of Genome

Sequence Data between Physicians, Researchers,

and Patients

Sitharthan Kamalakaran, Ph.D., Senior Member, Research

Staff, Philips Research North America

Patients’ genome sequences are informative for clinical care

over the patient’s lifetime and not just for the diagnosis at

hand. We present a web-accessible interface for clinicians to

integrate relevant patient genome data in their routine practice

through clinically-framed queries.

11:00 Targeted Next Generation Sponsored by

Sequencing in FFPE Tumor Samples:

Distilling High Quality Information from Low

Quality Samples

Sachin Sah, Senior Scientist, Diagnostics Research

Development, Asuragen, Inc.

SuraSeq™ PCR-based enrichment procedures enable accurate

and sensitive mutation detection from nanogram inputs of

challenging FFPE tumor DNA. Case studies will be presented

that highlight the use of complementary NGS platforms and

novel bioinformatics for discovery and confirmation studies.

11:30 Transitioning New Technologies from the Bench to the Bedside: Direct Fetal Testing Using Circulating

Cell-Free DNA

Allan T. Bombard, M.D., CMO, Sequenom

This presentation will address clinical test implementation of new tests in the US, using circulating

cell-free DNA for noninvasive

prenatal testing (NIPT) of fetal aneuploidy from maternal plasma as an example.

12:00 Moving Genomic Screening to the Clinic: Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara Crews Finley Chair in Medical Genetics; Professor and Chair,

Department of Genetics; Director, Heflin Center for Genomic Sciences, University of Alabama at Birmingham

Since the sequencing of the human genome there has been an expectation that a flood of advances would find their

way to the clinic, and, indeed, the pace of translation of genomics to clinical application is accelerating. It is likely that the future of

medical care will evolve by the convergence of two disruptive technologies – that of information science and genomics, which, in a

sense can be viewed as one and the same.

12:30 pm Close of Symposium

Featured Presentations

Genomically-Supported Diagnostic and

Drug Reposition Strategies out of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center

for Applied Genomics, Children’s Hospital of

Philadelphia

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

Moving Genomic Screening to the Clinic:

Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara

Crews Finley Chair in Medical Genetics;

Professor and Chair, Department of Genetics;

Director, Heflin Center for Genomic Sciences,

University of Alabama at Birmingham

Reasons to Attend

• Hear keynote presentations from Dr. Hakon

Hakonarson of CHOP and Dr. John Iafrate of MGH

• Find out how to transition genomic

screening to the clinic

• Discover evolving approaches to

mutation detection

• Explore data management and analysis solutions

• Learn the role of pharmacogenomics in

patient care

• Network with genomic thought leaders

• Par ticipate in interactive, problem-solving

breakout discussions

TriConference.com

February 11-15 • Moscone North Convention Center • San Francisco, CA

2013

Molecular Med

Tri-Con

Premier Sponsors:

2 Genomics in Medicine

Plenary Keynotes 2013 Sponsors

Wednesday, February 13 8:00 – 9:40 am

Personalized Oncology – Fulfilling the Promise for

Today’s Patients

In honor of the 20th anniversary of the Molecular Medicine Tri-conference, CHI and

Cancer Commons will present a plenary panel on Personalized Oncology. Innovations

such as NGS and The Cancer Genome Atlas have revealed that cancer comprises

hundreds of distinct molecular diseases. Early clinical successes with targeted

therapies suggest that cancer might one day be managed as a chronic disease using

an evolving cocktail of drugs. Representing all five conference channels, Diagnostics,

Therapeutics, Clinical, Informatics, and Cancer, a panel of experts will lead a highly

interactive exploration of what it will take to realize this vision in the near future.

Moderator: Marty Tenenbaum, Ph.D., Founder and Chairman, Cancer

Commons; Prominent AI Researcher; Cancer Survivor

Tony Blau, M.D., Professor, Department of Medicine/Hematology and

Adjunct Professor, Department of Genome Sciences, University of

Washington; Attending Physician, Seattle Cancer Care Alliance; Co-

Director, Institute for Stem Cell and Regenerative Medicine, University of

Washington and the Program for Stem and Progenitor Cell Biology at the

UW/FHCRC Cancer Consortium; Founder and Scientific Officer, Partners

in Personal Oncology

Sarah Greene, Executive Director, Cancer Commons

Laurence Marton, M.D., Adjunct Professor, Department of Laboratory

Medicine, University of California San Francisco; former Dean of

Medicine, University of Wisconsin

Jane Reese-Coulbourne, MS, ChE, Executive Director, Reagan-Udall

Foundation for the FDA; former Board Chair, Lung Cancer Alliance;

Cancer Survivor

Anil Sethi, CEO, Pinch Bio; HL7 Pioneer and Health Informatics

Entrepreneur

Joshua Stuart, Ph.D., Associate Professor, Department of Biomolecular

Engineering, University of California Santa Cruz

Thursday, February 14 8:00 – 9:40 am

Plenary Keynote Panel: Emerging Technologies &

Industry Perspectives

This session features a series of presentations on emerging and hot technologies in

diagnostics, drug discovery & development, informatics, and oncology. Interactive

Q&A discussion with the audience will be included.

Moderator: To be Announced

Gregory Parekh, Ph.D., CEO, Biocartis

Kevin Bobofchak, Ph.D., Pathway Studio Product Manager, Elsevier

Jeremy Bridge-Cook, Ph.D., Senior Vice President, Research &

Development, Luminex Corporation

Panelist to be Announced, Remedy Informatics

Harry Glorikian, Managing Partner, Scientia Advisors, LLC

Lynn R. Zieske, Ph.D., Vice President, Commercial Solutions, Singulex, Inc.

Sponsored by

Premier Sponsors:

Corporate Sponsors:

Molecular

Corporate Support Sponsors:

TriConference.com 3

Conference Programs:

Feb 13-15

Diagnostics Channel

Molecular Diagnostics

Personalized Diagnostics

Cancer Molecular Markers

Circulating Tumor Cells

Digital Pathology – NEW

Companion Diagnostics – NEW

Therapeutics Channel

Mastering Medicinal Chemistry

Cancer Biologics

Clinical and Translational Science

Clinical Channel

Oncology Clinical Trials

Clinical and Translational Science

Clinical Sequencing – NEW

Informatics Channel

Bioinformatics in the Genome Era

Integrated R&D Informatics and Knowledge Management

Cancer Channel

Cancer Molecular Markers

Circulating Tumor Cells

Predictive Pre-Clinical Models in Oncology – NEW

Oncology Clinical Trials

Cancer Biologics

Symposia*:

Feb 11-12

Targeting Cancer Stem Cells

Genomics in Medicine – NEW

Point-of-Care Diagnostics

Quantitative Real-Time PCR – NEW

Next Generation Pathology

Partnering Forum*:

Feb 11-12

Emerging Molecular Diagnostics

Short Courses*:

Feb 12

1:30-4:30pm

SC1 Identification & Characterization of Cancer Stem Cells

SC2 Commercialization Boot Camp: Manual for Success in

the Molecular Diagnostics Marketplace

SC3 NGS Data and the Cloud

SC4 Best Practices in Personalized and Translational

Medicine

SC5 Latest Advances in Molecular Pathology

SC6 Regulatory Approval of a Therapeutic & Companion

Diagnostic: Nuts & Bolts

SC7 PCR Part I: qPCR in Molecular Diagnostics

SC8 Data Visualization

SC9 Methods for Synthesis & Screening of Macrocyclic

Compound Libraries

5:00-8:00pm (Dinner)

SC10 PCR Part II: Digital PCR Applications and Advances

SC11 Sample Prep and Biorepositories for Cancer Research

SC12 Next-Generation Sequencing in Molecular Pathology:

Challenges and Applications

SC13 Strategies for Companion Diagnostics Development

SC14 Patient-Derived Cancer Tissue Xenograph Models

SC16 Microfluidics Technology and Market Trends

SC17 Open Cloud & Data Science

Get the best 5-day value! Our All Access

Packages is a convenient, cost-effective way

to attend each aspect of Molecular Med

TRI-CON 2013. Package includes access to

1 Symposium or Partnering Forum, 2 Short

Courses and 1 Conference Program.

TRI-CON All Access Package

*Separate reg required with a la carte pricing

Co-located Event

4 Genomics in Medicine

Inaugural Genomics in Medicine

Monday, February 11

7:30 am Registration and Morning Coffee

8:25 Chairperson’s Opening Remarks

Screening for Rare and

Difficult to Diagnose Diseases

8:30 KEYNOTE PRESENTATION:

Genomically-Supported Diagnostic and

Drug Reposition Strategies out

of Academia

Hakon Hakonarson, M.D., Ph.D., Director, Center for Applied

Genomics, Children’s Hospital of Philadelphia

This talk will discuss genomic strategies applied in academia

to identify subsets of patients who, based on their genetic

make-up, are predicted to have a favorable response profile to

drugs that come from reposition opportunities.

9:00 Evolving Approaches to Mutation Detection in

Rare Diseases

Tom Scholl, Vice President, Research & Development,

Integrated Genetics, LabCorp

Emerging trends in this field that include the expansion of

content in clinical tests to include many loci and increased

clinical sensitivity by expanding numbers of mutations detected

or whole gene sequencing will be presented.

9:30 From Raw Sequencing Data to

Functional Interpretation

Daniel MacArthur, Ph.D., Group Leader, Analytic and

Translational Genetics Unit, Massachusetts General Hospital

This presentation will discuss the key lessons learned

from large-scale sequencing studies in both common and

rare diseases with a particular focus on finding mutations

underlying severe muscle diseases.

10:00 Coffee Break with Exhibit and Poster Viewing

10:30 Providing Whole Genome Sequencing in the Clinic

David Dimmock, M.D., Assistant Professor, Pediatrics,

Medical College of Wisconsin

This presentation will focus on advances in the implementation

of genome wide sequencing in clinical practice. It will address

counseling and consent issues specific to testing children.

Specifically, it will highlight the challenges of execution in the

acute care setting.

11:00 Clinical Utility of Whole Exome Sequencing

Christine M. Eng, M.D., Professor, Department of Molecular

and Human Genetics, Baylor College of Medicine

This presentation will discuss the role of whole exome

sequencing in the diagnostic evaluation of patients with

challenging phenotypes of genetic etiology. Examples of

clinical utility, directed medical care, and cost-effectiveness

of the whole exome approach to clinical diagnostics will be

presented.

11:30 A Neuronal Carnitine Deficiency Hypothesis

for Autism

Arthur L. Beaudet, M.D., Henry and Emma Meyer Professor

and Chair, Department of Molecular and Human Genetics,

Baylor College of Medicine

We have published a paper entitled “A common X-linked

inborn error of carnitine biosynthesis may be a risk factor for

nondysmorphic autism” (PMID: 22566635). We propose a

neuronal carnitine deficiency hypothesis as one risk factor

or cause for autism whereby 10-20% of autism might

be preventable.

12:00 pm Luncheon Presentation

(Sponsorship Opportunity Available) or Lunch on

Your Own

Predictive Tests for

Improved Patient Outcomes

1:25 Chairperson’s Remarks

1:30 Implementation of Personalized Healthcare into

Clinical Practice: Lessons Learned

Kathryn Teng, M.D., FACP, Director, Center for Personalized

Healthcare, Cleveland Clinic

Integrating a pharmacogenetics program into clinical practice

requires a vision for the future of healthcare and a roadmap to

reach that vision. Pioneering the road to achieving this vision

has brought challenges and has allowed for the creation of

solutions that might be applied universally.

2:00 Molecular Profiling of Tumors to Select Therapy

in Patients with Advanced Refractory Tumors

Ramesh Ramanathan, M.D., Medical Director, The Virginia

G. Piper Cancer Center Clinical Trials

This presentation will discuss molecular profiling of tumors

using IHC, CGH and whole genome/exome sequencing of

tumors to find actionable targets for therapy. Clinical trials

and case reports of patients treated by this approach will

be presented.

2:30 Sponsored Presentations (Opportunities Available)

3:00 Refreshment Break with Exhibit and

Poster Viewing

3:30 Gene Panels vs. Whole Exome Sequencing in

Cancer Molecular Testing

Madhuri Hegde, Ph.D., FACMG, Associate Professor, Senior

Director, Emory Genetics Laboratory, Department of Human

Genetics, Emory University School of Medicine

TriConference.com 5

Individualized Care for Improved Outcomes

4:00 Next Generation Sequencing and

Cancer Diagnostics

Phil Stephens, Ph.D., Vice President, Cancer Genomics,

Foundation Medicine

Foundation Medicine has developed FoundationOne™, a

CLIA-certified, comprehensive cancer genomic test that

analyzes routine clinical specimens for somatic alterations in

189 relevant cancer genes. Experience with the initial 1,000

consecutive patients will be presented.

4:30 KEYNOTE PRESENTATION:

Clinical Cancer Genotyping – Snapshot

John Iafrate, M.D., Ph.D., Assistant Professor,

Pathology, Harvard Medical School; Assistant

Pathologist, Massachusetts General Hospital

The challenges and opportunities of implementing a broad

genotyping assay in routine clinical management of cancer

patients will be discussed. Snapshot was launched over 3

years ago at the Massachusetts General Hospital, with the

goal of providing all cancer patients with a genetic fingerprint

to guide therapeutic decisions. Lessons learned will be

outlined, and a roadmap to effectively move testing forward

into the Next Gen sequencing era.

5:00 Breakout Discussions (See Web for Details)

6:00 Close of Day

Tuesday, February 12

8:00 am Morning Coffee

Data Management and Analysis

8:10 Chairperson’s Remarks

8:15 Under the Hood of the 1000 Genomes Project

Mark A. DePristo, Ph.D., Associate Director, Medical

and Population Genetics Analysis, Broad Institute of MIT

and Harvard (on behalf of The 1000 Genomes Project

Consortium)

This presentation discusses the evolution of the nextgeneration

sequencing (NGS) data underlying the public

1000 Genomes Project resource, from some of the earliest

technologies of 2009 to today’s state-of-the-art data. It

will also highlight key NGS analytic advances originating

from the Project.

8:45 Delivering Genomic Medicine: Challenges

and Opportunities

Heidi L. Rehm, Ph.D., FACMG, Assistant Professor,

Pathology, BWH and Harvard Medical School; Director,

Laboratory for Molecular Medicine, Partners Healthcare

Center for Personalized Genetic Medicine

This talk will cover the speaker’s experience in offering clinical

sequencing to patients, from disease-targeted panels to whole

genome analyses as well as supporting the interpretation

and delivery of those results to physicians. It will also cover

approaches to data sharing within the community.

9:15 From Sequence Files to

Sponsored by

Physicians Report and the Tools

Needed to Get There

Martin Seifert, Ph.D., CEO,

Genomatix Software

Providing actionable biology from NGS data in a report useful

to the practicing clinician is difficult. Ensuring the report is

accurate, reproducible, and reflects the biology of the patient

is an even larger task. We will show examples of Genomatix’

approach to these issues and how we successfully ensure a

secure, accurate, and reproducible report, bridging the gap

from sequencer to clinician.

9:30 Rapid Identification of

Sponsored by

Disease Causative Mutations

Ali Torkamani, Ph.D., Co-Founder & CSO,

Cypher Genomics

Recent successes in clinical genome sequencing have

highlighted the potential for sequencing to greatly improve

molecular diagnosis and clinical decision-making. However,

these successes have relied upon large bioinformatics teams

and in-depth literature surveys. We will demonstrate how the

Cypher Genomics software service can quickly return a small

set of well-annotated genetic variants most likely to contribute

to a patient’s disease.

10:00 Coffee Break with Exhibit and

Poster Viewing

Getting Genomic Testing to Clinic

10:30 Sequence Data on Demand: Access,

Visualization and Communication of Genome

Sequence Data between Physicians, Researchers,

and Patients

Sitharthan Kamalakaran, Ph.D., Senior Member, Research

Staff, Philips Research North America

Patients’ genome sequences are informative for clinical care

over the patient’s lifetime and not just for the diagnosis at

hand. We present a web-accessible interface for clinicians to

integrate relevant patient genome data in their routine practice

through clinically-framed queries.

11:00 Targeted Next Generation Sponsored by

Sequencing in FFPE Tumor Samples:

Distilling High Quality Information from Low

Quality Samples

Sachin Sah, Senior Scientist, Diagnostics Research

Development, Asuragen, Inc.

SuraSeq™ PCR-based enrichment procedures enable accurate

and sensitive mutation detection from nanogram inputs of

challenging FFPE tumor DNA. Case studies will be presented

that highlight the use of complementary NGS platforms and

novel bioinformatics for discovery and confirmation studies.

NEW

TriConference.com 6

Recommended Programs:

Main Conference

• Personalized Diagnostics

Short Courses

• NGS Data and the Cloud

• PCR Part I: qPCR in Molecular Diagnostics

• NGS in Molecular Pathology

• PCR Part II: Digital PCR Applications and Advances

11:30 Transitioning New Technologies from the Bench to the Bedside: Direct Fetal Testing Using Circulating

Cell-Free DNA

Allan T. Bombard, M.D., CMO, Sequenom

This presentation will address clinical test implementation of new tests in the US, using circulating cell-free DNA for noninvasive

prenatal testing (NIPT) of fetal aneuploidy from maternal plasma as an example.

12:00 Moving Genomic Screening to the Clinic: Next Steps

Bruce R. Korf, M.D., Ph.D., Wayne H. and Sara Crews Finley Chair in Medical Genetics; Professor and Chair,

Department of Genetics; Director, Heflin Center for Genomic Sciences, University of Alabama at Birmingham

Since the sequencing of the human genome there has been an expectation that a flood of advances would find their

way to the clinic, and, indeed, the pace of translation of genomics to clinical application is accelerating. It is likely that the future of

medical care will evolve by the convergence of two disruptive technologies – that of information science and genomics, which, in a

sense can be viewed as one and the same.

12:30 pm Close of Symposium

7 Genomics in Medicine

Hotel Information

Reserve your hotel and save $100 off

your conference registration*

*You must book your reservation under the Tri-Conference

room block for a minimum of 4 nights at the Marriott or the

Intercontinental Hotel. One discount per hotel room.

Conference Venue:

The Moscone North Convention Center

747 Howard Street

San Francisco, CA 94103

http://www.moscone.com

Please visit TriConference.com to make your

reservations online or call the hotel directly to

reserve your sleeping accommodations.You will

need to identify yourself as a Molecular Med Tri-Con

attendee to receive the discounted room rate with

the host hotel. Reservations made after the cut-off

date or after the group room block has been filled

(whichever comes first) will be accepted on a spaceand

rate-availability basis. Rooms are limited, so

please book early.

Sponsorship &

Exhibit Opportunities

CHI offers comprehensive sponsorship packages which include presentation

opportunities, exhibit space and branding, as well as the use of

the pre and post-show delegate lists. Signing on early will allow you to

maximize exposure to hard-to-reach decision makers.

Breakfast & Luncheon Presentations

Opportunities may include a 15 or 30-minute podium presentation

during the main agenda. Boxed lunches are delivered into the main

session room, which guarantees audience attendance and participation.

Packages include: exhibit space, on-site branding, and more.

Invitation-Only VIP Dinner/Private Receptions

Sponsors will select their top prospects from the conference preregistration

list for an evening of networking at the hotel or at a choice

local venue. CHI will extend invitations and deliver prospects. Evening

will be customized according to sponsor’s objectives.

Exhibit

Exhibitors will enjoy facilitated networking opportunities with 3,000

highly-targeted delegates at the overall event. Speak face-to-face with

prospective clients and showcase your latest product, service, or solution.

Inquire about additional branding

opportunities, including our

Valentine’s Day Soiree sponsorship!

Looking for additional ways to drive leads to

your sales team? CHI can help!

We offer clients numerous options for custom lead generation programs

to address their marketing and sales needs, including:

• Live Webinars

• White Papers

• Market Surveys

• Podcasts and More!

For sponsorship & exhibit information, please

contact:

Companies A-K

Jon Stroup, Manager, Business Development

781-972-5483 • jstroup@healthtech.com

Companies L-Z

Joseph Vacca, Manager, Business Development

781-972-5431 • jvacca@healthtech.com

How to Register: TriConference.com

reg@healthtech.com • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

Please use

keycode GDX F

when registering!

short Courses (Tuesday, Feb 12)

1 Short Course $695 $395

2 Short Courses $995 $695

Diagnostics Channel

P1 Molecular Diagnostics

P2 Personalized Diagnostics

P3 Cancer Molecular Markers

P4 Circulating Tumor Cells

P5 Digital Pathology– NEW

P6 Companion Diagnostics– NEW

Informatics Channel

P13 Bioinformatics

P14 Integrated R&D

Informatics &

Knowledge Management

Cancer Channel

P3 Cancer Molecular Markers

P4 Circulating Tumor Cells

P15 Predictive Pre-Clinical Models

in Oncology – NEW

P10 Oncology Clinical Trials

P9 Cancer Biologics

Clinical Channel

P10 Oncology Clinical Trials

P11 Clinical and

Translational Science

P12 Clinical Sequencing– NEW

Therapeutics Channel

P7 Mastering Medicinal

Chemistry Summit

P9 Cancer Biologics

P11 Clinical and

Translational Science

S1 Targeting Cancer Stem Cells S2 Genomics in Medicine S3 Point-of-Care Diagnostics S4 Quantitative Real-Time PCR S5 Next Generation Pathology

SC10 PCR Part II: Digital PCR Applications and Advances

SC11 Sample Prep and Biorepositories for Cancer Research

SC12 Next-Generation Sequencing in Molecular Pathology:

Challenges and Applications

SC13 Strategies for Companion Diagnostics Development

SC14 Patient-Derived Cancer Tissue Xenograph Models

SC16 Microfluidics Technology and Market Trends

SC17 Open Cloud & Data Science

Afternoon

SC1 Identification & Characterization of Cancer Stem Cells

SC2 Commercialization Boot Camp: Manual for Success in the Molecular Diagnostics Marketplace

SC3 NGS Data and the Cloud

SC4 Best Practices in Personalized and Translational Medicine

SC5 Latest Advances in Molecular Pathology

SC6 Regulatory Approval of a Therapeutic & Companion Diagnostic: Nuts & Bolts

SC7 PCR Part I: qPCR in Molecular Diagnostics

SC8 Data Visualization

SC9 Methods for Synthesis & Screening of Macrocyclic Compound Libraries

SOURCE:

http://www.triconference.com/uploadedFiles/MMTC/13/MMTC_Symposium_Final_GDX.pdf

Read Full Post »


Genome-Wide Detection of Single-Nucleotide and Copy-Number Variation of a Single Human Cell(1)

Reporter, Writer: Stephen J. Williams, Ph.D.

Most tumors exhibit a level of diversity, at the cellular, histologic, and even genetic level (2).  This genetic heterogeneity within a tumor has been a focus of recent research efforts to analyze the characteristics, expression patterns, and genetic differences between individual tumor cells.  This genetic diversity is usually manifested as single nucleotide variations (SNV) and copy number variations (CNV), both of which provide selection pressures in both cancer and evolution.

As cancer research and personalized medicine is focused on analyzing this tumor heterogeneity it has become pertinent view the tumor as a heterogeneous population of cells instead of as a homogenous mass.  In, fact, studies have suggested that cancer cell lines growing on plastic in culture, even though thought of as clonogenic, can actually display a varied degree of expression differences between neighboring cells growing on the same dish.  Indeed, cancer stem cells show an asynchronous cell division, for example a parent CD133-positive cell will divide into a CD133-positive and a CD133-negative cell(3). In addition, the discovery that circulating tumor cells (a rare population of circulating cells in the blood) can be prognostic of outcome in cancer such as inflammatory breast cancer(4), it is ever more important to develop methods to analyze single cell populations.

Harvard University researchers, Dr. Chenghang Zong, Sijia Lu, Alec Chapman and Sunney Xie developed a new amplification method utilizing multiple annealing and looping-based amplification cycles (MALBAC)(1).   A quasilinear preamplification process is used on pictograms of DNA genomic fragments (form 10 to 100 kb) isolated from a single cell.   This is performed to reduce the bias associated with nonlinear DNA amplification.  A series of random primers (which the authors termed MALBAC primers, constructed with a common sequence tags) are annealed at low temperature (0 °C). PCR rounds produce semiamplicons.  Further rounds of amplification, after a step of looping the amplicons, result in full amplicons with complementary ends.  When the two ends hybridize to form the looped DNA, this prevents use of this loop structure as a template, therefore leading to a close-to–linear amplification.    The process allows for a higher fidelity of DNA replication and the ability to amplify a whole genome.  The amplicons are then sequenced either by whole-genome sequencing methods using Sanger-sequencing to verify any single nucleotide polymorphisms.  This procedure of MALBAC-amplification resulted in coverage of 85-93% of the genome of a single cell.

As proof of principle, the authors used MALBAC to amplify the DNA of single SW480 cancer cells (picked from a clonally expanded population of a heterogeneous population (the bulk DNA).  Comparison of the MALBAC method versus the MDA method revealed copy number variations (CNV) between three individual cells, which had been picked from the clonally expanded pool. Their results were in agreement with karyotyping studies on the SW480 cell line.  Meticulous quality controls were performed to limit contamination, high false positive rates of SNV detection due to amplification bias, and false positives due to amplification or sequencing errors.

Interestingly, the authors found 35 unique single nucleotide variations which h had occurred from 20 cell divisions from a single SW480 cancer cell.  This resulted in an estimated 49 mutations which occurred in 20 generations, yielding a mutation rate of 2.5 nucleotides per generation.  In addition, the authors were able to map some of these mutations on various chromosomes and perform next-gen sequencing (deep sequencing) to verify the nucleotide mutations and found an unusually high purine-pyrimidine exchange rate.

In a subsequent paper, investigators from the same group at Harvard used this technology to sequence 99 sperm cells from a single individual to study genetic diversity created during meiotic recombination, a mechanism involved in evolution and development(5).

Reference:

1.            Zong, C., Lu, S., Chapman, A. R., and Xie, X. S. (2012) Science 338, 1622-1626

2.            Cooke, S. L., Temple, J., Macarthur, S., Zahra, M. A., Tan, L. T., Crawford, R. A., Ng, C. K., Jimenez-Linan, M., Sala, E., and Brenton, J. D. (2011) British journal of cancer 104, 361-368

3.            Guo, R., Wu, Q., Liu, F., and Wang, Y. (2011) Oncology reports 25, 141-146

4.            Giuliano, M., Giordano, A., Jackson, S., Hess, K. R., De Giorgi, U., Mego, M., Handy, B. C., Ueno, N. T., Alvarez, R. H., De Laurentiis, M., De Placido, S., Valero, V., Hortobagyi, G. N., Reuben, J. M., and Cristofanilli, M. (2011) Breast cancer research : BCR 13, R67

5.            Lu, S., Zong, C., Fan, W., Yang, M., Li, J., Chapman, A. R., Zhu, P., Hu, X., Xu, L., Yan, L., Bai, F., Qiao, J., Tang, F., Li, R., and Xie, X. S. (2012) Science 338, 1627-1630

Other related posts on this website regarding Cancer and Genomics include:

Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz

Identifying Aggressive Breast Cancers by Interpreting the Mathematical Patterns in the Cancer Genome

Read Full Post »

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