CLARITY Challenge

Medicine is on the threshold of a revolution in patient care. With important insights emerging daily about the genetic basis of disease, and the cost of sequencing an individual’s genome plummeting from more than $3 million to $1,000 or less in the past decade and a half, genomic information is beginning to become a part of everyday care.

This new capability opens possibilities for designing tailored, life-long strategies to maintain people’s health and treat disease based on their genetic makeup and knowledge of environmental factors that may affect their health.

Yet, while the speed of genomic sequencing is rapidly increasing, our understanding of how to apply the new information has not advanced as quickly. How reliable are these data, and how do we deliver the information in an understandable way to physicians or patients to help improve patient care?

The answer lies in creating standardized methods for analyzing, interpreting, reporting and, ultimately, using genomic information in a clinical setting.

This is why Boston Children’s Hospital has launched the CLARITY Challenges.

Each Challenge is led by a multidisciplinary team of specialists at Boston Children’s Hospital and Harvard Medical School with expertise in rare disease, genetics, genomics and bioinformatics, and invites submissions from medical and research centers around the world. Submissions are reviewed by an independent panel of judges.

CLARITY I: Rare Disease

Our first CLARITY Challenge, launched in January 2012, called on the international community to find a genetic basis for disorders in three families identified by The Manton Center for Orphan Disease Research. Of 40 teams submitting applications, 30 were selected to compete and received genomic sequences for the three affected children and their families and tasked to provide an analysis, interpretation and report suitable for use in a clinical situation.

The Institutional Review Board (IRB) at Boston Children’s Hospital approved the protocol, allowing competitors to access de-identified materials and records from the three families.

In all, 23 teams completed the Challenge. The results, announced November 2012 and published in full in the journal Genome Biology in 2014, solved at least one family’s genetic mystery while demonstrating the variability from center to center in costs, efficiency and scalability of sequencing, as well as the quality of the clinical reporting and patient-consenting process. The Challenge results also underscored the need for medical expertise to bring meaning to the genomic data.

The winning team—led by the Brigham and Women’s Hospital Division of Genetics with members from Massachusetts General Hospital (Boston), Partners Laboratory for Molecular Medicine (Boston), Brown University (Providence, RI) and Utrecht University (Netherlands)—was awarded $15,000. Two finalist teams were awarded $5,000 each: the University of Iowa and a German team comprised of Genomatix (Munich), CeGaT (Tübingen) and the Institute of Pathology at University Hospital of Bonn (Bonn).

CLARITY Undiagnosed

CLARITY Undiagnosed brings international, crowd-sourced genomic interpretation to five families who have undiagnosed disease. Up to 30 teams will compete to solve each patient’s diagnosis, receiving whole genome sequence data for each patient and key family members, along with clinical summaries and, at the discretion of the families, short videos of the patient.

Independent of the actual Challenge, a production team from the forthcoming documentary “Undiagnosed” proposes to document the progress and results of CLARITY Undiagnosed. Competing teams may wish to agree to be filmed, or to self-document their own process and submit video footage to the documentary team. The filming and the independent movie are not affiliated with Boston Children’s and the hospital has no responsibility for any matter related to the “Undiagnosed” film and expressly disclaims any such responsibility.

Families will not be available for interviews—either by contestants or the media—for the duration of the Challenge.

Frequently Asked Questions

How is CLARITY Undiagnosed different from the original CLARITY Challenge?
Sequencing analysis has gotten more sophisticated and standardized. As a result, CLARITY Undiagnosed will focus less on the technical “pipeline” elements of sequence analysis and more on providing clear, defensible and actionable results for the patients and families. New for this Challenge, contestants may receive short video presentations of the patients and family members.

How many of the five cases are we expected to work on?
Teams will be given access to all five patient cases and anticipated to work on each.

How will contestants be judged?
The competing teams will be judged based on the reports submitted for the patients in the Challenge. Scoring will consider the thinking process, scientific knowledge, clinical relevance of the findings and the clarity of communications to the doctor and patient.

Can we submit functional studies with our report?
If you can do such studies in the allotted time frame, go for it! However, we will not be providing additional materials (e.g., serum, fibroblasts, etc.) for your experiments.

Can we speak with the families?
That is not possible, but we may provide contestants with short videos to give you a glimpse of each family, if the family has voluntarily provided a video. Teams that attempt to reach out to the families will be immediately disqualified.

Can we give you a question to ask a family?
It depends on the situation. We will consider all questions and review them on a case-by-case basis. If you have a question for a family, please submit it to If it’s decided that your question is relevant, it will be shared with the other contestants together with the answer.

I can only provide reports for some of the cases. What do I do?
We understand. Simply provide as much information as you can. We are expecting the teams to show their ability to think through a case and conceptualize recommendations. Even if a diagnosis is not found, exploring ideas and possible care plans and next steps can be meaningful for families. Teams will not be penalized for an incorrect diagnosis or case conceptualization. Attempts to cover all cases will be looked upon favorably by the judging panel.

What if we disagree with the “correct” answer?
We understand that sometimes clinicians and researchers disagree. The judges’ decisions will be final, but we welcome continued discussion and collaboration.

I am a bioinformaticist and don’t interact with patients. Can I enter? Am I at a disadvantage?
In the first CLARITY Challenge, multidisciplinary teams tended to do better in the competition. However, we encourage all capable teams to apply.

I am/have a patient with an undiagnosed genetic condition. Can I/my patient be part of a future CLARITY Challenge?
We suggest you contact the Manton Center for Orphan Disease Research at as a first step.

I did a great job but didn’t win. How can I find out why?
Please email the conference organizers with your questions after the conference. We will also submit the full Challenge proceedings for publication in a medical journal.

Is the filming related to the Challenge?
Patients for the CLARITY Challenge were identified through a documentary film in the making, titled “Undiagnosed.” You do not need to agree to be filmed to enter the Challenge and separate permission will be obtained for the filming. The filming is not part of the Challenge.

If I enter the Challenge, will I be part of the film?
Independently of the Challenge, you may be approached by the filmmakers about giving separate consent to be included in the movie. Giving consent does not guarantee that you will be included, and you may also choose not to be filmed. The filmmakers would like to include some footage of the working teams to show the collaborative way to approach undiagnosed patients, and you may be offered an opportunity to be part of this by the production team. If you give consent to be filmed, the filmmakers may request permission to send a cameraperson to film some of your process. They may also provide you with an opportunity to make a video diary, should you wish, upon your acceptance into the Challenge. Your decision whether or not to participate in the filming is completely independent of your participation in the Challenge and will have no bearing whatsoever on the outcome of the Challenge.

The documentary is going to focus on the experience and the collaboration of the teams, not “winners vs. losers.” The teams that are selected for CLARITY are there because they are good, so the goal is to reflect that.

Am I liable for what I write in the report?
The report is considered as “think tank” and not as medical recommendations to be followed by the patients, similar to a “grand rounds” about the case. The ideas offered by the teams will be shared with the patient’s own medical doctor, who may make recommendations if she or he believes that it will benefit the patient.