Genome-wide clinical-grade interpretation

We are getting very close to the point that genome-scale sequence is available for clinical use. But will we know how to process and interpret it for such clinical applications?

Harvard Medical School, Children’s Hospital Informatics Program, and Harvard Medical’s School Center for Biomedical Informatics, the Partners Center for Genetics and Genomics, and the Harvard Medical School Center for Computational Genetics will hold a working meeting on December 7th and 8th, 2010 at the Countway Library on the Harvard Medical School campus. The purpose of this meeting is to directly address the challenges of providing consistent and clinically useful information to physicians and their patients based on large-scale genome sequencing. This meeting will focus on developing a "pre-competitive space" where industry collaborates earlier and more often to accelerate the clinical benefit from next-generation sequencing. Attendees are from clinical laboratory, sequencing, electronic health record companies as well as governmental and academic groups. This is a free but limited attendance meeting so please contact me if you are interested.

Holding our breath for this diabetes risk

A recent study exemplifies the leverage that can be obtained from mining existing, public data sets to further our national healthcare agenda. As described by the NY Times, our colleague John Brownstein obtained data from the Centers for Disease Control and Prevention (CDC) and U.S. Environmental Protection Agency (EPA) and found a consistent relationship between the amount of air pollution (particulate matter in the air) and population risk for diabetes (after correcting for the usual suspects such as income and ethnicity). This and other large-scale populations studies such as the one we recently reported by Atul Butte suggest that we might be insufficiently including the larger environment in our study of the diabetic plague that has afflicted us.

It also suggests that we have insufficiently taken advantage of freely available public data to pursue relevant and timely medical research.

What does a Harvard Medical or School of Public Health student think when she first tours the library?

Circulation and reference staff gave tours and orientations to the incoming medical and public health students and just wrote down every question that the students asked. The students volunteered these questions, and they were not prompted. The word cloud below represents their questions. It will be interesting to see if this cloud will change with time for this group. (Hat tip Wendy Brown)

Do you get to read your own genetic data?

My distinguished colleague Patrick Taylor and genetics/bioethics researchers Wylie Burke and Laura Beskow engaged in an interesting debate that can be listened to at TheScientist.

What are they checking out at Harvard Medical School?

Enterprising souls at the circulation desk of the Countway Library of Medicine have provided this Twitter feed on the books being checked out (http://twitter.com/hrvrd_med_out). See how studious your colleagues are?

Marco Ramoni

My dear and brilliant colleague, Marco Ramoni, died unexpectedly last week. This is not the venue for personal recollections, so I provide the academic sketch here as well as an invitation for contributions to a prize in his honor.

Marco Ramoni, PhD, Associate Professor and Medicine at Harvard Medical School and research faculty at Children’s Hospital, Boston and Brigham and Women’s Hospital. Most recently the Director, Biomedical Cybernetics Laboratory, Harvard Medical School, Director, NLM Fellowship in Biomedical Informatics, Children's Hospital Informatics Program., and Associate Director of Bioinformatics, Harvard - Partners Center for Genetics and Genomics. He was also the Director of the course “Biomedical Informatics” at the Harvard-MIT Division of Health Sciences and Technology, core faculty of the course Genomic Medicine at Harvard Medical School and a member of the curriculum committee of the Cellular and Molecular Medicine track of the Medical Physics and Medical Engineering graduate program at Harvard-MIT Division of Health Sciences and Technology. He was co-founder of Bayesware LLC, a software company developing machine-learning programs based on Bayesian methods.

He received a PhD in Biomedical Engineering and a BA in Philosophy (Epistemology) from the University of Pavia (Italy) and his postdoctoral training from McGill University, Montreal (Canada). He held academic and visiting positions at the University of Massachusetts, the University of London (United Kingdom), the Knowledge Media Institute (United Kingdom), and the University of Geneva (Switzerland). He was author of well over 100 publications in genetics, biomedical informatics, statistics and artificial intelligence.

The AMIA Board of Directors, at the urging of Dr. Ramoni’s colleagues, devoted friends and family, this week established the Marco Ramoni Fund, to support an award in Marco’s honor to be presented each year at the AMIA Summit on Translational Bioinformatics (TBI). The award will be presented to the author who submits a paper at the meeting that best exemplifies the spirit and scholarship of Marco F. Ramoni, PhD. To read more about Dr. Ramoni and the new Marco F. Ramoni Fund, click here.

Let our data go

In principle we have access to our own healthcare data. In practice, it is frequently laborious, costly and at least inconvenient and sometimes impossible. In that context as noted by my colleague Keith Strier, we have some good news from the federal government.

In the very first PCHRI conference, when I facilitated the business section, one of the few truly memorable take-aways for me was coming to the conclusion that what we really needed was a “download” button on EHRs. It seemed so simple, but unachievable. Yet, here we are, the first major public initiative to install a download button. It’s nice to see if come full circle.

http://govhealthit.com/newsitem.aspx?nid=73961

Perhaps the government will mandate that all developers and vendors of electronic health records must follow suit.

Should your email be archived?

Who will make sure that the pearls of your scholarship, scattered throughout your email and other electronic files will survive and be studied? Or should such digital ephemera be allowed to be composted in the big electronic bit bucket in the sky? These and other questions will be addressed June 9th at the Harvard Digital Scholarship Summit.

What about the environment?

Hundreds of millions of dollars have been spent on comparing the frequencies of genetic variants in disease-afflicted and control populations to suss out the genetic basis of diseases, common or rare. The results for diseases with diabetes have been mixed which despite the high concordance of this disease in identical twins raises yet again the question of the role of the environment in the etiology of diabetes. Of course, we know that the inherited component of diabetes risk is contingent on environmental factors (notably diet) but these are much harder to quantify and moreover there is a universe of environmental risks that is potentially much larger than the entirety of the genome. So how to go about capturing more of the environmental risk as it pertains to real human beings (as opposed to petri dish or rodent studies)?

Atul Butte at Stanford shows us how, through the lens of informatics, systematic approaches can be taken to understand the environmentally-borne determinants of our disease burden. He leverages one of the most admirable public national studies of US citizens, the NHANES study. Butte and colleagues performed analyses analoguously to genome wide association studies but instead examined each of the chemicals (e.g. pesticides, heavy metals, vitamin metabolites) measured in the urine and blood of the members of the NHANES groups comparing cases of diabetes vs. controls. As summarized in the figure below, after comparing multiple groups they found a consistent increased risk of diabetes with PCB and pesticide derivatives and a decreased risk with some carotene derivatives (related to vitamin A). Although, just as for their genome-wide analogues, the results of this Environment Wide Association Study (EWAS) should be taken with due caution, they add to a growing array of methodologies that provide a complement to conventional randomized and controlled studies.

Looking SHARPly at electronic health records

Earlier, I commented about some concerns about current implementations of electronic health records and aspirations for a very different model that would be far more nurturing of innovation. John Halamka was kind enough to craft a summary of a recent award we just received for a proposal to bring these aspirations to practice.

Science Meets Nature

Who's Gonna Pay for these Journals?

Town Hall Meeting: Who’s Gonna Pay for these Journals?

2:00-3:30 PM

Thurs., April 8, 2010

TMEC, Walter Amphitheater

Harvard Medical School

Scholarly Communication is broken.

Your access to articles in Brain Research, Tetrahedron Letters, Cell, Nature publications, and other leading journals in every discipline is paid for to the tune of millions of dollars per year by Harvard libraries.

Journal costs are skyrocketing and free market processes are failing to control costs--STM publishers can charge what they want without regard to value because they have a monopoly on the content that you have given them.  More and more you will be seeing "This article is not included in your organization's subscription " because libraries can no longer afford to buy back the content that has been freely given to the publishers. Commercial publishers make up to 40% profit on work produced here at Harvard and other research institutions. How can we establish some control over these costs and at the same time make it easier for you to regain control of your rights to use your own work?

Come to a Town Meeting and discuss what we can do to fix scholarly communication!

Free access app for open access content

We have just released a new iPhone application in collaboration with PloS Medicine and with the leadership of the Healthmap team (particularly John Brownstein) that allows you to read, browse and share content from PLoS Medicine including their features such as "collections". More to come in this vein from this and other knowledge sources in the near future.

Libraries can be catalysts for translational research

It's an open secret that most major academic health centers are lagging in providing their researchers with state of the art knowledge in the computational techniques required to analyze data sets with tens of thousands of variables. The exponential growth of the generation of these data sets over the last decade has far outstripped the ability of the average post-doctoral student to analyze them. With the advent of libraries whose curatorial taste and reference expertise now extends to vast biomedical data sets and their analysis, we are well positioned to catalyze the diffusion of bioinformatics expertise through the research community. One such example is heralded here at the Harvard Clinical and Translational Science Center.

Making new the old

In this era of fungible electronic sources of data, there remain unique sources of scholarly materials developed in the course of the conduct of biomedical research. One of these is the Countway's Center for the History of Medicine (CHoM) which has just inaugurated its new electronic public face. There, you can learn which of CHoM's holding have been recently featured in the Smithsonian Magazine, a new initiative for digitizing rare books, or the availability of a new important collection.

We will miss our book-filled bookshelves (at least for a while)

This article on the proliferation of incompatible electronic book formats and digital rights management (DRM) standards for book content is a stark reminder that much of what is digital is incompletely archived, if at all. This is particularly the case for our personal collections. I have some favorite novels and text books which I can still pick off my shelves in my office months or decades after I first purchased them. Until that unlikely day that all digital books are sold without DRM or that one DRM/encoding is adopted by all electronic book vendors, I will have to hope against hope that the vendor of the e-book I also use will remain in business. Otherwise, I will have to regularly repurchase all the books I purchased in electronic form every few years. Or just reread those older and less evanescent paper-based books.

the new conditions of the Harvard Medical School promise to be as nearly ideal as the forethought of man can plan

or so it says in this 1905 article from Popular Science now available to all through the Popular Science archive viewer (courtesy of Google). Worth reading also for many wonderful quotes including "A medical student so trained [ in regularly reading selected up-to-date publications] in the use of medical literature can hardly be content to depend on antiquated text-book knowledge in his practise in after years." Amen. But do our students currently know how to (and have the culture) get up to date genetic and genomic relevant knowledge from the web? Perhaps our libraries can continue to lead in this regard.

What the Tell-Tale Heart Tells Us About Healthcare

At the end of his short story, Edgar Allen Poe's haunted murderous protagonist lets loose in front of the unsuspecting police officers:

"Villains!" I shrieked, "dissemble no more! I admit the deed! -- tear up the planks! -- here, here! -- it is the beating of his hideous heart!"

It is this story that inspired the title of a paper we published a few years ago on how we could detect the increase (and subsequent decrease) of myocardial infarctions coincident with the rise and fall of the use of Vioxx. This investigation relied solely on the informational byproducts of healthcare delivery. This weekend a Senate report on the risk of Avandia and what was known by GSK came to light. This resonated because we had recently published an article in Diabetes Care about the rapid identification of an increased risk of myocardial infarction with Avandia in patients with diabetes mellitus as compared to other drugs, even drugs in the same class, such as Pioglitazone. Whereas the current headlines are about what the pharmaceutical company knew or dissimulated, there is a broader question that needs addressing: Should every healthcare system not be instrumented so that the clinical leaders of these systems should know whether there are unexpected changes in the risks and health status of their patient populations?

Often, the state of clinical practice is compared unfavorably to the practice of commercial air travel, but what remains underemphasized is that as a system, we are flying blind. There is no local, regional or national air-traffic-controller-equivalent for the healthcare system. Should not the local hospital, and Department of Public Health be the first to know if there is about to be a local health collision or crash? Should not such local surveillance systems run in parallel to regional and national systems? Do we not need multi-level redundancy and open communication to avoid tens of thousands of unnecessary deaths? Further, even as the federal government becomes more aware of the need of such instrumentation, we all expect that our local healthcare systems and health authorities should know of any untoward health trends. Perhaps healthcare systems will start to compete on being able to provide timely and localized health trend data to their customers. Unfortunately right now, the major investments in such health market intelligence is to the payors (i.e. the insurers) who quite reasonably want to know what are the local risks, performance and trends for each of their contracts. Will it take regulation or market competition to make such data extraction and return to patients a matter of course? Let's hope we do not have to wait for a post-mortem Poe'esque orgy of recrimination to find out.

No iTunes-equivalent for Google

Google and the Authors Guild and the Association of American Publishers had hoped to create a one-stop shop for a wide array of published works. The Department of Justice has just ruled that the current proposal does not pass muster. Whether or not this helps or hinders dissemination or scholarship appears to be a matter of some controversy.

Biomedical science is not a game for the young?

The National Institutes of Health have helpfully posted summary information about their funding patterns. It is much more revealing of the training patterns and mentoring of young investigators at our academic centers than any specific NIH policy. It is evident that whatever your terminal degree, your age at first R01 is 42-44, a full 10 years older than the age of first R01 in 1970. PhD's only are 2 years younger on average than MD's and MD-PhD's are remarkably no older than the MD's (which was not the case in 1970). What does this say about the capability of our research workforce to be energetically innovative? Are we drawing from the right pool of investigators or is there something fundamentally wrong in the institutionalized career path leading to an R01?

Who are the right practictioners of medicine?

This report from Haiti is a reminder that doctors are not always the answer to a healthcare need. We might be well-served by a national discussion of what are the properties of healthcare practitioners that we believe we are seeking to maximize and whether these are well matched to our needs as a society and as patients. It is a discussion which will also inform budgets.

Positive Peer Pressure

Can we use Internet-borne viral messages to counter biological viruses? Our very own Ben Reis is recognized by HHS Secretary Kathleen Sebelius for his Facebook application:

The “I’m a Flu Fighter” Facebook application takes users through four steps. In the first step, “Choose My Character,” users choose between a superhero, a doctor, a virus behind bars, or a cartoon syringe to represent themselves as a flu fighter. Then, users set their status by sharing whether they got the flu vaccine or plan to, and how it was (Could be better, Fine, Good, Great!). Next, users can send invites to their friends challenging them to get vaccinated. Lastly, users are taken to a page with resources about flu such as the flu vaccine locater. The visibility of users’ information as Flu Fighters is controlled by users through their privacy settings.