St. Jude Cloud Provides Model For Cancer Collaboration

St. Jude Cloud Cancer Collaboration

When researching a rare disease with many subtypes driven by diverse and distinct genetic alterations, data sharing is key. Samples acquired by a single institute, a single research initiative, or even a single nation may lack sufficient power for genomic discovery and clinical correlative analysis, and the mass of raw data from whole genome sequencing presents challenges. 

Which is why we were proud to partner with St. Jude Children’s Research Hospital and Microsoft to create a solution: a cloud-based, data-sharing ecosystem that has proved to be a model for harmonized genetic data and collaboration across the pediatric cancer community. 

Since the initial announcement of the partnership in 2018, more than 1.25 petabytes of data have been incorporated into the St. Jude Cloud, including:

  • 12,104 whole genomes;
  • 7,697 whole exomes; and 
  • 2,202 transcriptomes, from more than 
  • 10,000 pediatric cancer patients and long-term survivors, and 
  • 800 pediatric sickle cell patients

As reported recently in the journal Cancer Discovery, this makes it the largest publicly available genomic data resource for pediatric cancer, and it has already helped advance research. 

For example, Camille Keenan and colleagues gained new insight into a rare C11orf95 fusion in ependymoma by uploading and analyzing their RNA-Seq samples using the RNA Classification workflow on St. Jude Cloud. The Cancer Discovery paper includes additional use cases that classify 135 pediatric cancer subtypes by gene expression profiling and map mutational signatures across 35 pediatric cancer subtypes. 

How does the St. Jude Cloud work? Raw and curated genomic data, analysis and visualization tools are structured into three inter-connected apps: 

  • Genomics Platform, for accessing data and analysis workflows; 
  • PeCan, a Pediatric Cancer Knowledgebase for exploring a curated knowledgebase of more than 5,000 pediatric cancer genomes; and 
  • Visualization Community, for exploring published pediatric cancer genomic or epigenomic landscape maps, and for visualizing user data using ProteinPaint or GenomePaint. 
St Jude Cloud Visual Pipeline

Common use cases, such as assessing the recurrence of a rare genomic variant or the expression status of a gene of interest, are built into these apps, eliminating the need to download data and perform custom analyses. To enable researchers with little to no formal computational training to perform sophisticated genomic analysis, we also developed eight end-to-end analysis workflows designed with a point-and-click interface for uploading input files and graphically visualizing the results. 

“Effective sharing of genomic data and a community effort to elucidate etiology are…critical to developing effective therapeutic strategies,” the Cancer Discovery paper authors wrote. “The complementarity amongst the three apps within the St. Jude Cloud ecosystem enables the optimal use of computational resources so that researchers can focus on innovative analyses leading to new insights.”

The project leverages Microsoft Azure data storage and our open and flexible DNAnexus Portals™ workspace to create a secure environment compliant with all of the major data privacy standards (HIPAA, CLIA, CGP, 21 CFR Parts 22, 58, 493, and European data privacy laws and regulations). 

As the paper authors note, St. Jude Cloud currently hosts genomic data generated primarily by St. Jude studies, but they envision it will serve as a collaborative research platform for the broader pediatric cancer community in the future. 

“User-uploaded data can be analyzed and explored alongside the wealth of curated and raw pediatric genomic data on St. Jude Cloud, and deposition of user data into St. Jude Cloud requires minimal effort. In this regard St. Jude Cloud represents a community resource, framework, and significant contribution to the pediatric genomic sequencing data sharing landscape.” 

2020 Vision: What Have We Learned?

2020 Vision: Lessons Learned

The year 2020 certainly didn’t go as planned. But it was educational. We all had a crash course in infectious disease biology, trial-by-fire lessons in virtual meeting etiquette, and eye-opening lessons in the difficulties of homeschooling and trying to maintain a work-life balance within the same few walls for days, weeks, and months at a time.

At DNAnexus, we also learned a few things — about our customers and their evolving needs, about our capacity to pivot and adapt to meet those needs, and about our ability to be even more creative than ever in delivering novel solutions to this new norm. Here are some of our top lessons.

1. Easy, reliable access is key. One of the biggest challenges people have faced while working from home is accessing the data, applications, and compute resources they need. With the majority of employees suddenly using the VPN every day, network bottlenecks and slow download times can quickly become a chronic problem. And in many cases, some data and resources may simply not be accessible to users who aren’t on-premise. Luckily, the DNAnexus Platform and the Cloud Workstation App proved to be lifesavers, enabling secure, fluid, reliable collaboration and sharing with partners and peers around the globe. 

2. You love to learn. We developed a suite of free bioinformatics courses available to users of varying experience levels, and many of you were eager to brush up on your skills, or learn new ones. The online curriculum, which was selected with input from our customers, was so popular that we will be continuing it into the new year. We’re especially excited about the first one — Demystifying AI & ML in Biomedical Research — which will be held January 28. Add it to your calendars now! You can save your seat here.

3. Going virtual means going global. Although we missed the chance to spend some time connecting with our customers and the science/technology community in person, we were excited for the opportunity to expose our research to the wider world, as most conferences went virtual. The American Society of Human Genetics (ASHG), for instance, featured a host of great science from our own team as well as many of our customers and research partners. We also got to flex our creative muscles designing some fun virtual ‘booths’ and resource pages.

4. Opportunity sometimes knocks on the door of disaster. Watching the fevered pace of early research into SARS-CoV-2, David Fenstermacher, our Vice President of Precision Medicine and Data Services, wondered: Could COVID power a new era of precision medicine, moving it beyond oncology? Infectious disease seems a strong candidate for a precision medicine approach, he argued, due to the high variability between patients, and being able to link genetic profiles to clinical outcomes would be extremely useful when developing diagnostics and formulating treatment plans. By stratifying patients based on genetic information, healthcare providers and government decision-makers could adopt more rational and effective surveillance, containment, and treatment strategies.

5. Science doesn’t stop. Nor does innovation. In fact, we may have gotten even more innovative in order to keep scientific discoveries coming apace. Scrolling through our blog, you can find story after story about improvements to our platform, new applications, and examples of some of the amazing research it is enabling. We were proud to be recognized as a top workplace for innovators, and we look forward to continuing to carry out our mission of revolutionizing the use of genomic and other omic information in healthcare in 2021.

Deciphering the TCR Repertoire

TCR Repertoire

Between the 4th and 19th centuries AD, knowledge of how to read and write Egyptian hieroglyphs was essentially nonexistent. Not until 1799 when French officers found the Rosetta Stone, was there any hope to translate this complex script. With the help of the stone, scholars were able to crack the complex code of hieroglyphics, and gain a deeper understanding of ancient Egyptian life. 

Just like the Rosetta Stone was critical to understanding ancient Egyptian mysteries, the immune repertoire is key to unlocking insights about an individual’s immune response to their environment. Thankfully, advances in next-generation sequencing and computational biology have made translating the immune repertoire a modern reality. 

What is the immune repertoire and why is it important? 

Specialized cells of the immune system, such as macrophages, T-cells, and B-cells, work together to identify threats in the body, and activate a coordinated and complex immune response. An important part of the immune response occurs when a T-cell detects a threatening target and receptors on the T-cell bind to the enemy cell, or antigen. The T-cells then duplicate many times in a process called clonal expansion, and remain in the body to quickly respond when the same antigen appears again.  

Each unique receptor on the T-cell recognizes only a single antigen, and this range is encoded by a fixed number of gene segments. Thus, the T-cell receptor (TCR) repertoire holds the key to understanding the diversity of the immune system and how it responds to disease-causing antigens. By sequencing the TCR repertoire and learning the genetic code of the cells, researchers can begin to understand which antigens those particular T-cells have targeted, build a disease profile that an individual has encountered, and determine whether a particular vaccine or immunotherapy drug may be effective. This powerful information can be used to develop diagnostic tests, create therapeutic products, and predict responses to immunotherapies. 

This week, immune profiling company, MIODx launched ClonoMapTM Immune Profiler, an analysis and biomarker discovery platform that allows researchers to probe the immune system and better understand how an individual’s T-cells can make them susceptible to disease or certain therapies, and how that can change over time. 

A healthy individual’s immune system consists of a vast TCR repertoire, in the order of 109 cells, so the ability to scale up computational resources is crucial. Powered by the scalable and flexible DNAnexus Titan Platform, ClonoMapTM Immune Profiler enables researchers to conduct powerful analysis by incorporating large datasets from multiple and longitudinal studies, integrating metadata, and processing multiple versions of analysis in parallel to generate and test hypotheses on the relevance of TCR samples as biomarkers. 

The MIODx team is at the cutting edge of TCR repertoire research. By empowering researchers with the analytical tools to study the genetic code of T-cells, gain an understanding of the antigens that the T-cells target, and study how the immune system changes over the course of an individual’s lifetime, MIODx is laying the groundwork to translate the TCR repertoire into actionable insights to inform human health. 

Read more about MIODx and their ClonoMapTM Immune Profiler here.