A step forward: Consent for Clinical DNA Sequencing at the Iowa Institute of Human Genetics

During a recent podcast on Mendelspod.com, Colleen Campbell at the Iowa Institute of Human Genetics (IIHG) described the process of introducing pharmacogenomic testing and clinical exome sequencing at the University of Iowa. The project started small, but included pharmacogenomic testing for clopidogrel, as well as whole exome sequencing (WES). At IIHG, WES is intended for diagnostic odyssey patients; patients with a large list of differential diagnoses (where WES is more economical than multiple, individual genetic tests); and patients with atypical presentations of disease. (Today, WES provides a diagnostic answer about 25% of the time.)

As part of the process, patients complete this plain language informed consent form that explains the benefits and risks associated with genetic testing. The form lets patients decide how to receive information about incidental and secondary findings. More importantly, the consent form lets patients easily contribute their health information for future research. Unless patients opt-out, DNA samples and genetic data can be:

  • Compared with genetic information from others to improve future tests
  • Stored for future studies
  • Placed in a national repository (without identifying information)
  • Used to develop future products and services
  • Published in research studies (results, without identifying information)
  • Made into cell lines (from the DNA blood sample)

The consent form also includes lets the patient opt-in so that IIHG can use patients’ genetic information in future research studies (beyond the original purpose for the test).

IIHG has done an exemplary job involving an entire community to integrate genomics into clinical practice. By educating hospital staff, patients and the community, genomic medicine will slowly begin to take root.

Note: I would not be surprised to see IIHG presenting their results at conferences over the next year, including AHIMA, AMIA, ANIAASHG and HIMSS.

Paper: Big Desire to Share Big Health Data

health-data-sharing-model

Today I presented this paper about sharing personal health data at the 2014 AAAI Spring Symposium Series, hosted at Stanford University. The paper, co-authored with Melanie Swan, summarized the results of an online survey to gauge consumer attitudes toward sharing health information. Here’s the abstract:

Sharing personal health information is essential to create next generation healthcare services. To realize preventive and personalized medicine, large numbers of consumers must pool health information to create datasets that can be analyzed for wellness and disease trends. Incorporating this information will not only empower consumers, but also enable health systems to improve patient care. To date, consumers have been reluctant to share personal health information for a variety of reasons, but attitudes are shifting. Results from an online survey demonstrate a strong willingness to share health information for research purposes. Building on these results, the authors present a framework to increase health information sharing based on trust, motivation, community, and informed consent.

The take-home messages from the paper are:

  1. Consumers are willing to share health data under the right conditions.
  2. Education seems to play a strong role.
  3. Consumers want to be connected to their data.
  4. Develop models to encourage sharing. 

My favorite part of the talk was explaining how I repeated the survey using an online market research tool. Our respondents were extremely educated — 59% had a Master’s level education or higher — so I wondered if education played a role in their willingness to share. In less than two hours, I posted the survey and received 100 responses (compared with the nine months it took to receive 128 IRB-consented responses). This time, about 20% of the respondents had a Master’s level education or higher, still higher than the US average of 10%, according to the US Census Bureau. Nevertheless, overall attitudes toward sharing were similar. In particular, respondents who were not willing to share their health information tended to have little or no college experience. Although both surveys operated on convenience samples, the results suggest that education plays a role, perhaps because education can change our perception of the risks and benefits associated with sharing health data. Interestingly, these results and conclusions were similar to those found in a recent report published by the Health Data Exploration project sponsored by the Robert Wood Johnson Foundation. More information about this project:

The survey is ongoing! It takes just five minutes, so please add your voice here.

Autism Hackathon in San Francisco

This weekend I collaborated with Melanie Swan at the Autism Hackathon in San Francisco. Sponsored by Twilio and supported by Autism Speaks, this hackathon brought together 50+ developers and designers who created prototype applications for the autism community. At the end of the 24-hour event, a dozen teams presented 5-minute “pitches” for their ideas.

More here: http://www.autismspeaks.org/news/news-item/autism-speaks-and-twilio-team-hacking-autism

Our entry, “MindFlower,” is an “eLabor Marketplace for ASD Solvers.” Think about getting paid for solving puzzles like the ones in FoldIt–that’s the idea.

For more information about MindFlower, see these slides on slideshare.net

Note: MindFlower is just a concept, not an actual business or organization.

Image      (Image credit: Kimberly Pickard)

Restless Legs Syndrome and Niacin Study #2: Quantified Self Meetup in San Francisco

I will be presenting results from my second self-tracking study at the Quantified Self San Francisco meetup at Microsoft later tonight in San Francisco.

Experiment

By participating in this crowdsourced study on Genomera, I tested niacin supplementation as a potential treatment for Restless Legs Syndrome (RLS).

Methods

This experiment had two main differences from the first one. First, I tapered off my current medication, clonazepam, after ramping up with niacin. Second, I increased the daily niacin dose from 500mg to 2000mg, which meant that the ramp-up was also much longer.

RLS-Study2-Pickard.xls

I recorded some sliding scale measurements of RLS sensation, leg jerks, etc. in a spreadsheet (see above). Aggregated measurements are also available to Genomera’s members.

Results

Like the last experiment, niacin did not improve my RLS symptoms, even at the higher dose. However, RLS severity was less after tapering off clonazepam, perhaps due to the niacin. Since the first experiment, I also started taking an iron supplement to increase my ferritin level, which might also account for diminished RLS severity. As before, I saw my doctor after the experiment to discuss the results. We changed my medication to Mirapex, which is also commonly used to treat RLS. Compared to clonazepam, I feel more alert. The RLS symptoms remain under control, and amazingly, feeling returned to my sciatic nerve about one month ago–I can feel it all the way down to the top of my left big toe. I am unsure what this means, but after injuring my back 30 years ago it seems significant.

Finally, I wanted to mention that my psoriasis flared once I started taking niacin at 2.0g/day. Subsequently, I read several articles discouraging psoriatics from taking large doses of niacin.

Overall, this QS journey has been worth it. I learned more about my RLS, but more importantly, how to ask better questions that improved my health.

Link to slides on slideshare.net

 

Sage Synapse: A home for open medical data

Synapse

I just posted my 23andMe data to Sage Synapse, a collaborative space that allows scientists to share and analyze data together. After authenticating with Synapse, you can access the data here: https://synapse.sagebase.org/#Synapse:syn1444765

Here’s a short video introduction to the Synapse platform:

I will be adding more data to Synapse in the near future.

Trust, but verify

Working with 23andMe exome data: my CF allele and the need for verification

This informative blog post from Dr. Jung Choi at Georgia Tech discusses how to use free, publicly available bioinformatics tools to interpret new exome sequence data from 23andMe. The post includes a response from 23andMe in the comments.

Some of the bioinformatics tools that Dr. Choi uses are:

The post highlights the challenges of mapping gene-protein interactions when reporting results.

Jc_cftr_rpt

The Impact of Open Access and Social Media on Scientific Research

Jopm_logo

The Impact of Open Access and Social Media on Scientific Research

Summary: Participatory medicine flourishes where there is an unimpeded flow of information. Open and freely available access to medical research improves outcomes and empowers e-patients. Traditionally, research papers undergo peer review before publication. Two trends, open access and social media, are changing the peer review process.

I wrote this article to learn more about the peer review process. Since the article was peer-reviewed, I learned more than I expected. The article was recently published in the Journal of Participatory Medicine.

What is a Gene?

In an ongoing effort to unravel the mysteries of DNA, I recently completed a class at UC Berkeley, “Introduction to Genetic Analysis.” This essay, “What is a Gene?” was part of my final. Although the question could easily pass as a Zen koan, I gave it a shot.

What is a Gene?
 
To paraphrase Nature reporter Helen Pearson, ‘gene’ is not your typical four-letter word. Unlike most four-letter words whose definitions are well understood, the definition of a gene remains elusive. The more scientists learn about genes, the more the definition seems to fray around the edges. A question such as ‘How many genes are in this organism?’ is difficult to answer conclusively without a consistent description. In 2006, one research group examined the results of 77 experiments counting the number of genes in the human genome; none produced the same result (Liolios et al, 2006 doi:10.1093/nar/gkj145). From the smallest virus with three functional genes to humans with approximately 22,000, counting genes is challenging.

With roots in Mendel’s research on garden peas, the term “gene” has evolved from its original definition of a “unit of inheritance” to one that reflects advances in molecular biology. A commonly accepted definition is that a gene is a region of nucleic acid that specifies an RNA or protein. This definition encompasses both single- and double-stranded DNA and RNA. Exons, coding regions of DNA and RNA that are translated into protein sequences, are found in most, but not all genes. To incorporate a finding that proteins can be produced from non-coding exon regions, some geneticists have added “flanking regulatory elements” to this definition (Pesole, 2008 doi:10.1016/j.gene.2008.03.010). This addition incorporates genetic curiosities such as the lac operon, which allows bacteria to digest lactose. Newer definitions may emphasize functional products—counting proteins or RNA—rather than specific DNA loci. More precise definitions that apply to specific types of organisms, e.g., eukaryotes, seem inevitable.

After the discovery of the structure of DNA by Watson and Crick, mechanisms describing DNA replication, transcription and translation quickly followed. DNA, which functions as a “parts list” of molecular information, stores an organism’s functional repertoire. The addition of molecular information to biology provided a physical basis for understanding heredity, which in turn led to the surprising finding that organisms share many genes in common. This commonality has provided insight into the evolution of various species. Through the lens of evolution, genes exist to convert the molecular information stored in DNA into self-sustaining multicellular organisms. Organisms with adaptive genes transmit their genetic information to the next generation to ensure the successful propagation of the species.

In 1955, the year Watson and Crick’s paper appeared, Einstein was asked to define “light quanta,” or what are now commonly called photons. His response was:

All these fifty years of conscious brooding have brought me no nearer to the answer to the question, ‘What are light quanta?’ Nowadays, every Tom, Dick and Harry thinks he knows it, but he is mistaken. (Born, 1971 The Born-Einstein Letters)

In the ensuing fifty years, particle physicists arrived at a consensus describing photons (the so-called Standard Model). In genetics, the results from the Human Genome Project in 2000 provide a foundation on which to build future results. A clearer answer to the question ‘What is a gene?’ is emerging. The answer to this question will provide more accurate interpretations of the similarities and differences between individuals and species.

Genetics Guides on Genomera

Genomera

Along with Leila Jamal and Aaron Vollrath, I recently joined Genomera as a group guide in the genetics discussion group. Still in beta, Genomera enables personal health collaboration by providing a platform for crowdsourced health studies.

Genomera Interview

Thomas Pickard serves as an advisor to DIYgenomics, Althea Health, and the Coleman Research Group. He is Vice President of Marketing & Business Development at PACSGEAR, a company that integrates medical images with electronic health records. Previously, Thomas held roles at Emageon, eMed Technologies, and Thinking Machines.

  1. Tell us about your adventures in genetics.
     
    In the early 90’s, I learned a little about bioinformatics at MasPar, a company that sold supercomputers for research. The ‘ah ha’ moment came from reading George Church’s article about the Personal Genome Project in Scientific American, which advocated getting your genome sequenced as a “lifestyle choice” (!) Shortly afterwards, I began work on an MBA and finished research on the $1000 genome in 2009. Since then, I’ve been immersed in genomics and its implications for personalized medicine.
     
  2. Has genetic information shaped your life in any way? How do you foresee it affecting our lives in the next 5 years?
     
    On Genomera, a useful side-effect from the Restless Legs Syndrome and Niacin study was learning that my ferritin level was extremely low, which appears to have a genetic basis. Iron supplementation has made a difference, but more importantly, Genomera has allowed me to ask better questions. I have learned more about RLS in the past few months than I have in the past 20 years living with the disease. Over the next five years, we’ll all be able to ask better questions through the mining of genomic information.
     
  3. What studies would you like to see at Genomera?
     
    Genomera is unique because participants can elect to share genomic information as part of a study. As Genomera expands, I would like to see studies that analyze results and genetic variants across studies—a true game changer for personal health and wellness.