Bring Your Questions for Genetics Entrepreneur Anne Wojcicki

By Stephen J. Dubner
DESCRIPTIONAnne Wojcicki

Anne Wojcicki, a biotech analyst and biologist, is co-founder of the “personal genetics” company 23andMe — which, for a fee, will take a bit of your spit and map out your DNA to learn genealogical details as well as your risk factors for certain diseases. Clients can also join the company’s gene-themed social networks and share their genetic info with others. Sort of like Facebook for your innards.

Wired’s Adam Rogers wonders whether services like 23andMe could lead to “genetic hypochondria,” leaked genetic information, or a spike in preventive measures that some may consider extreme.

Wojcicki’s husband is a moderately well-known tech guy who, thanks to his wife’s work, learned that he has a genetic mutation that makes him more likely to get Parkinson’s disease.

Before starting 23andMe, Wojcicki spent 10 years in healthcare investing with a focus on biotech companies.

She has agreed to take your questions, so fire away in the comments section below. (I wonder what she thinks of a fat tax — that’s a tax on fat food, people, not fat people.) As with all Q&A’s, we will post the answers here shortly.

Addendum: Wojcicki answers your questions here.

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George Church and Craig Venter in One Room

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If You’ve Got Questions, Here’s Your Chance

August 03, 2009

The Freakonomics blog at the New York Times is accepting questions for 23andMe’s Anne Wojcicki. Head to the comments thread to post your question, and the answers will be posted there in about a week. Steven Dubner, in introducing the company’s genetic and social networking aspects, says it is “sort of like Facebook for your innards.”

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Cancer Stem Cells Make a Splash

August 14, 2009

In Cell, Eric Lander and his colleagues report on an approach to screen for compounds that selectively target cancer stem cells. Using that technique, they found that salinomycin, which has “selective toxicity for breast CSCs”, leads to a greater than 100-fold reduction in the amount of CSC, as compared to paclitaxel, a chemotherapy drug used to treat breast cancer. In the New York Times, Lander adds that this method gives “a potential for a real renaissance in cancer therapeutics.”

In discussing the Broad Institute paper, the Cancer Research UK’s Kat Arney also blogs about the theory and role of cancer stem cells. “The role of stem cells in cancer is still not crystal clear, and although there’s evidence they play a role in many types of cancer, they’re not always implicated,” Arney writes.

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This Week in Science

August 14, 2009

In this week’s issue of Science, there’s an interview with Margaret Hamburg, the new FDA Commissioner, about her views on the organization’s changing roles as well as her thoughts on how to bolster confidence in the agency. She says, “I hope a hallmark of my tenure as FDA commissioner is to establish that FDA is a science-driven agency and that, as we make critical regulatory decisions, we welcome and foster the input of all of our scientists and outside experts.”

San Francisco State University’s Michael Goldman reviews DNA: Promise and Peril, in which Linda McCabe and Edward McCabe talk about both the ethical issues and the potential of genomic medicine. Goldman is skeptical that the McCabes, medical geneticists at UCLA, aren’t against genetic determinism, as they say they are, because of the focus on epigenetics. “That simply pushes the problem one step back, by suggesting that when we can analyze the methylation and chromatin state or transcriptional activity of every gene, then we will be able to predict the future of each individual,” he writes. “It is not necessarily so.”

A policy forum article looks into consent issues surrounding biobank samples and information from children. The authors argue that when possible, access to this data should be preceded by their consent as adults. A story in our sister publication, GenomeWeb Daily News, has more.

A group led by Max Planck’s Matthias Mann used high-res mass spec to examine the extent of lysine acetylation across the entire human proteome. They identified 3,600 lysine acetylation sites on 1,750 proteins, finding that it “preferentially targets large macromolecular complexes involved in diverse cellular processes, such as chromatin remodeling, cell cycle, splicing, nuclear transport, and actin nucleation,” they say. They also found that acetylation can influence susceptibility of proteins to phosphorylation.

In other work, researchers studied the genetic basis of sleep duration, or how many hours a person needs a night. In the process of performing candidate gene resequencing, they identified a mutation in a transcriptional repressor, hDEC2-P385R, that is linked to shorter daily sleep times. Says a related perspective, “Molecular genetic approaches remain our best hope to find, without a priori assumptions, molecules that regulate the complex phenotype of sleep.”

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NCI’s caBIG Plans to Award $3.5M to Five In Silico Research Centers

August 10, 2009

Columbia University, Emory University, Georgetown University, Fred Hutchinson Cancer Research Center, and the Translational Genomics Research Institute have been notified they are “contingent” awardees under the National Cancer Institute’s “In Silico Research Centers of Excellence” program.

The NCI Center for Biomedical Informatics and Information Technology and SAIC-Frederick, an NCI contractor, announced the contracts in late July. The term “contingent” refers to the fact that SAIC-Frederick and the individual institutions still need to reach final contractual agreements, a spokesperson told BioInform.

According to a solicitation for the program issued last December [BioInform 01-02-09], SAIC-Frederick planned to award approximately five contracts worth a total of $3.5 million per year.

The program’s goal is to “empower in silico research” for large data sets that have been made available to the cancer community. In particular, the centers will perform hypothesis-driven research projects on data sets, including those that are part of the Cancer Biomedical Informatics Grid, or caBIG, according to the NCI announcement.

The directors of the five contingent in silico research centers are: Andrea Califano, professor of biomedical informatics at Columbia University; Joel Saltz, director Emory University School of Medicine’s Center for Comprehensive Informatics; breast cancer researcher Robert Clarke, who is professor of oncology, physiology and biophysics at Georgetown University; Martin McIntosh, principal investigator at the Fred Hutchinson Cancer Research Center’s Computational Proteomics Laboratory; and Will FitzHugh at The Translational Genomics Research Institute.

“The primary goal of the ISRC will be to add scientific value to the large-scale datasets developed as part of the caBIG program, and currently accessible through the caGrid,” the solicitation stated.

The centers will use tools developed as part of the caBIG program, as well as other open-source or commercial tools to “accomplish the desired goals of making novel discoveries” with the potential of advancing cancer’s mechanisms, treatment and prevention strategies.

The solicitation was open to academic or commercial organizations with “expertise in computational biology, informatics analysis, statistics, genomics, proteomics, or image analysis.”

In response to questions from applicants, SAIC-Frederick indicated that the $3.5 million total funding for the program is a “fixed price” that includes both indirect and direct costs and also includes all “anticipated costs” including hardware and software.

In response to a question about the use of proprietary software at the centers, SAIC-Frederick responded that proprietary software may be used “as long as the algorithms are publicly documented” and that any output does not require proprietary software to be read. The use of proprietary software “with licensing terms that are assigned to output” will not be approved for use, SAIC stated.

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Bioinformatics Pros: Labs Should Include Data Management in All Project Plans

August 14, 2009
By Vivien Marx

With large-scale second-generation sequencing-based projects taking hold, labs need to budget and plan for data management throughout a project’s timeline, an NIH official told BioInform this week.

Many researchers “totally underestimate issues around data management,” Joni Rutter, associate director of Human Population and Applied Genetics at the National Institute on Drug Abuse’s Division of Basic Neuroscience and Behavioral Research, told BioInform.

Rutter is the project officer for the Epigenomics Data Analysis and Coordination Center and spoke about general issues connected to data management, not issues particular to EDACC.

Scientists writing grants think first and foremost about their science and when fitting a project to a particular NIH budget, data-management resources “tend to be the first things to go” when cutting costs, she said.

With centralized data repositories such as EDACC, NIH is helping to be “more efficient” in managing scientific data, since repositories assist in fostering standards and formats for data deposit, she said.

At this year’s Intelligent Systems for Molecular Biology conference, Owen White of the University of Maryland School of Medicine, who directs the Human Microbiome Project’s Data Analysis and Coordination Center, shed some light on how such a center operates.

White noted that the DACC is not responsible for primary data submission, but helps each of the HMP centers handle -omics and clinical data in a “rapid response” fashion.

The data center’s “position,” White said, is to have the sequencing centers deposit data and metadata, to “not interfere, and [to] let the pipeline stream along.” Over time, “we will be structuring it” and doing “lots and lots of clean-up of the data,” he said.

Metadata is being collected, he said, for example, on sample prep methods, since that will “impact how the data will cluster” in downstream analysis, he said.

He and his group are also “encouraging, or some might call it policing,” which means monitoring data quality, assuring data is documented, and helping centers to resolve data-management issues.

“We’re constantly evaluating tools used by the centers and developing standards,” White said, adding that his group is developing a software repository and pipelines and making them available to scientists.

Change the World?

Data management is not only an issue for large, multi-center projects, however. Small labs, in particular, are quickly finding that data management is a core requirement for high-throughput experimental platforms.

While ads for second-generation sequencers tell scientists that the instruments are “going to change the world,” that change won’t happen unless researchers in traditional biochemistry or molecular biology labs can use the data, “and they can’t, “Anton Nekrutenko told BioInform during ISMB.

Nekrutenko is associate professor of biochemistry and molecular biology at Penn State University and co-PI for Galaxy, an open source bioinformatics data integration and analysis platform.

Data-intensive bioinformatics tasks that were once relatively rare are now “permeating every aspect of biology,” said James Taylor, a computational biologist at Emory University and Galaxy co-PI.

That development calls for “effective” methods of managing data, as well as introducing “more control, reproducibility, [and] transparency to data analysis,” he said.

Nekrutenko and Taylor organized the data and analysis management special interest group, or DAM-SIG, meeting at ISMB/ECCB. One focus of the sessions was on the need to standardize metadata. “I think that’s a very important aspect” of data management “to allow for “better, open interchange formats for understanding and querying experimental metadata across experiments,” Taylor said.

Metadata management plays a “very important” role in microbial and metagenomic projects and is still often an unsolved challenge, Nekrutenko said.

Some tools are coming online to help researchers handle metadata, though. At ISMB, Philippe Rocca-Serra, a researcher at the European Bioinformatics Institute, outlined his group’s “standards-supportive infrastructure,” for annotating metadata in the ISA-Tab format with ontologies and according to standardized reporting guidelines so scientists can manage multi-domain experimental metadata.

A beta version of the software suite, called ISA Tools, was released in late July here.

The suite includes ISAcreator for annotating and editing metadata and an app called ISAconverter for converting ISA-Tab files to formats suitable for submission in public repositories.

Annotation is Key

Other observers view accurate and thorough annotation as the key to effective long-term data management.

The research value of -omics data “correlates directly with how precise, exhaustive, and consistent” its annotation is, Tom Beatty told BioInform via e-mail this week.

Beatty, a principal researcher at business technology consulting firm CSC who specializes in life science and healthcare consulting within the firm’s Emerging Practices Group, said that a community-wide, wiki-style approach to annotation could be useful.

Likewise, Sanjeev Wadhwa, director of CSC’s Life Sciences R&D Practice, told BioInform via e-mail that semantically enriched wiki content, which can be processed and interpreted by wiki-based ontology infrastructures, “will provide intuitive means to collaboratively create, organize, and retrieve knowledge.”

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CDC/NIH Workshop Releases Personal Genomics Recommendations

August 14, 2009
By a GenomeWeb staff reporter
NEW YORK (GenomeWeb News) – A government-led panel has issued a list of recommendations related to the clinical utility and clinical validity of personal genomic tests, enhancing knowledge about these tests, and developing standards for these tests, according to a report in the journal Genetics in Medicine.

The report is the product of a December 2008 workshop led by the National Institutes of Health and the Centers for Disease Control and Prevention, and it included a number of other stakeholders in government, academia, and the business world.

The working group developed five broad recommendations for ways to “enhance the foundation” for using personal genomics in order to improve health.

It said that efforts to develop and implement standards for personal genomics should be expanded to include transparent criteria for analytic standards, clinical standards on the selection of genetic variants, data interpretation, and the calibration and evaluation of risk distributions.

A multidisciplinary research agenda also should be implemented, the group advised, that could help to develop the personal genomics field. Beyond biological studies that could point to therapeutic and preventive interventions, this research could include epidemiologic studies for risk characterization, particularly those on gene-gene and gene-environment interactions. Also needed are clinical and population studies to assess the effectiveness of genetic information for consumers and providers, as well as health services research that assesses the uptake of evidence-based practice into routine care, and outcomes research, the group said.

The working group also said that public health surveillance and the assessment of cost-effectiveness, as well as current federal genomic initiatives in translational research should be enhanced.

Knowledge should be synthesized based on standardized formats and evidence-based processes in order to summarize and update information on genetic associations and to document their clinical validity and clinical utility, the group advised. They also said that this information should be translated in an accessible fashion and should be spread among consumers, providers, and policy makers.

The evidence threshold for using personal genomic information in clinical practice and disease prevention should be considered by independent panels, according to the group.

Setting the bar for evidence too low for clinical utility and clinical validity may allow a diffusion of genomic discoveries into practice, but there may not be adequate information on their effectiveness, the group said. But, placing the bar for evidence too high could result in tests with high validity and utility but with lower financial incentive for innovation by developers.

For these reasons, the group noted, “extra caution” is needed when developing how much evidence is necessary for clinical utility and validity.

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Fielding Questions on 23andMe and Lifestyle, GINA, Snickering, and More

August 13, 2009

Readers at the New York Times’ Freakonomics blog have grilled 23andMe’s Anne Wojcicki. There, she discusses the impact of genetic testing on people’s lifestyle, GINA, epigenetics, and why genetic counselors “snicker” at 23andMe. For the last, Wojcicki says that the medical community in the past has been reluctant to shift to “individual empowerment” (she cites over-the-counter pregnancy tests and anonymous HIV tests) and that people can handle knowing their genetic information. “Individuals with access to their APOE allele (which is strongly correlated with age of onset of Alzheimer’s) are quite capable of handling that information in a healthy way,” she says.

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In Nature

August 13, 2009

There’s a slew of papers in the early online edition of Nature on stem cells. “Five studies show that disabling p53, an essential tumour-suppressor protein, improves the efficiency of stem-cell production,” says a News and Views authored in part by Scott Lowe. “Are these results a ‘heads up’ that cancer cells and stem cells are disturbingly similar?”

Shinya Yamanaka is lead author on one paper that used knockdown, microarray, and functional analysis to show that lack of p53 expression promotes iPS cell generation in human cells, and that the p53-p21 pathway “serves as a barrier not only in tumorigenicity, but also in iPS cell generation.” Another paper shows that the Ink4/Arf locus, which encodes three potent tumor suppressors, is a barrier for iPS cell reprogramming. Other exciting work adds more insight.

In this week’s issue, more research looks into the chromatin state of embryonic stem cells. In work led by Miguel Ramalho-Santos at UCSF, scientists show that the chromatin remodeling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Down-regulating Chd1 leads to accumulation of heterochromatin, the write, while embryonic stem cells lacking Chd1 are no longer pluripotent. A News and Views article has more.

In Nature Chemical Biology, Caltech scientists have come up with a method to selectively label proteins in specific cells in mixtures of cells. Using non-naturally occurring amino acids that contain azide groups in their side chains, they show that these are only incorporated into proteins in cells that express a mutant of the methionyl-tRNA synthetase enzyme. “When the authors added this amino acid to a co-culture of normal and mutant Escherichia coli cells, only the mutants were subsequently tagged with an alkyne-containing affinity reagent or fluorescent dye,” says Andrew Mitchinson in a News and Views piece.

“Biology has just gotten a new set of standards for graphically representing biological information,” says a blog post at Scientific Blogging, pointing to a paper published this week in Nature Biotechnology on the new Systems Biology Graphical Notation standard. “SBGN consists of three complementary languages: process diagram, entity relationship diagram and activity flow diagram. Together they enable scientists to represent networks of biochemical interactions in a standard, unambiguous way,” the authors, led by The Systems Biology Institute’s Hiroaki Kitano and EMBL-EBI’s Nicolas Le Novère, say in the abstract.

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