Breaking News
September 22, 2018 - Concern over fussy eating prompts parents to use non-responsive feeding practices
September 22, 2018 - Novel mathematical approach uncovers existence of unsuspected biological cycles
September 22, 2018 - Cancer Research UK invests £14 million to transform London into cancer biotherapeutics hub
September 22, 2018 - Scientists predict how well the body will fight lung cancer by analyzing immune cell shapes
September 22, 2018 - New outbreak of rare eye disease identified in contact lens wearers
September 22, 2018 - Iterum Initiates SURE 2 and SURE 3 Phase 3 Clinical Trials of IV and Oral Sulopenem in Complicated Urinary Tract and Complicated Intra-abdominal Infections
September 22, 2018 - Research finds divide in dental health accessibility between city and regional areas
September 22, 2018 - Premature babies show better brain development when fed breast milk, finds study
September 22, 2018 - Novel system uses AI to detect abnormalities in fetal hearts
September 22, 2018 - UNC scientists reveal new approach to prevent obesity and diabetes
September 22, 2018 - CWRU receives NIH grant to learn how non-coding genes contribute to spread of colorectal cancer
September 22, 2018 - Scientists better understand influenza virus and how it spreads
September 22, 2018 - Scientists to focus on length of time when a person is alive and healthy
September 22, 2018 - Study shows positive financial impacts of Medicaid expansion for low-income Michigan residents
September 22, 2018 - Innovative approach for developing vaccine against most prevalent human malaria parasite
September 22, 2018 - Inhibiting NF-kB improves heart function in a mouse model of Duchenne muscular dystrophy
September 22, 2018 - Introducing new EMR system may affect several aspects of clinic workflow
September 22, 2018 - Study finds why some human genes are more popular with biomedical researchers
September 22, 2018 - Finding epigenetic signature appears to predict inflammation risk in serious type of IBD
September 22, 2018 - Researchers develop light-based technique to measure very weak magnetic fields
September 22, 2018 - UAB researchers study dysfunction of the immune system associated with NSAID carprofen
September 22, 2018 - QIAGEN and DiaSorin launch automated, CE-marked workflow for high-throughput TB screening
September 22, 2018 - Researchers identify new genetic disorder in a human patient
September 22, 2018 - Cardiac MR With Contrast Feasible in Developing World
September 22, 2018 - Daily low-dose aspirin doesn’t reduce heart-attack risk in healthy people
September 21, 2018 - Children with asthma found to be disadvantaged in education and future occupation
September 21, 2018 - Interaction of chemical slurry and ancient shale in fracking wastewater causes radioactivity
September 21, 2018 - Scientists use mice to study transmission of Lyme disease bacteria by infected ticks
September 21, 2018 - Researchers find that sample size is key factor determining accuracy of study results
September 21, 2018 - Study shows how the drive to eat overpowers the brain’s signal to stop
September 21, 2018 - 30 Million Americans Now Have Diabetes
September 21, 2018 - Thousands of breast cancer gene variants engineered and analyzed
September 21, 2018 - The current fellowship interview process is cumbersome — Stanford researchers have a better idea
September 21, 2018 - Progenitor cells for human bone and cartilage have been identified
September 21, 2018 - Study reveals new therapeutic target for pediatric tumor-associated intractable epilepsy
September 21, 2018 - SLU’s College professor receives NIH grant to develop I-TEST project
September 21, 2018 - DermTech completes enrollment in clinical study to assess DNA damage and reversal
September 21, 2018 - Grieving patients treated with talk therapy have lower risk of suicide and psychiatric illness
September 21, 2018 - NIH and FDA call for eliminating involvement of RAC in human gene therapy experiments
September 21, 2018 - New system uses algorithm to convert 2D videos into 3D printed ‘motion sculptures’
September 21, 2018 - Sea squirt model reveals key molecules in dopaminergic neuron differentiation
September 21, 2018 - Effective management of neonatal abstinence syndrome requires coordinated ‘cascade of care’
September 21, 2018 - Refugees seek care for wounds of war
September 21, 2018 - Under the sea, in an octopus’ garden on ecstacy
September 21, 2018 - Eating foods with low nutritional quality ratings linked to cancer risk in large European cohort
September 21, 2018 - Giving kids honest information about water consumption may help them make healthy choices
September 21, 2018 - Horwitz Prize Awarded for Work on Hormones
September 21, 2018 - CHMP issues positive opinion supporting use of Trelegy Ellipta in broader group of COPD patients
September 21, 2018 - Scientists discover new molecules that work together to remove unwanted DNA
September 21, 2018 - Dr. Fenella France to deliver 2019 Plenary Lecture
September 21, 2018 - New research finds that MHC-II molecules have more influence on tumors than MHC-I
September 21, 2018 - Researchers study effects of cardiac cycle in simple learning task
September 21, 2018 - FDA takes new steps to address opioid crisis by approving Opioid Analgesic Risk Evaluation and Mitigation Strategy
September 21, 2018 - Positive Barhemsys Phase 3 Treatment Data Published in Anesthesia & Analgesia
September 21, 2018 - Celiac Disease Screening: MedlinePlus Lab Test Information
September 21, 2018 - Autism linked to egg cells’ difficulty creating large proteins
September 21, 2018 - Tweaking nuclear pores could provide new avenue to battle against cancer
September 21, 2018 - Experts warn health care providers to slow down in allowing smart pill in patient care settings
September 21, 2018 - MoreGrasp reports breakthrough development of grasp neuroprosthetics activated by thought control
September 21, 2018 - Study reveals new way to target HER2-negative metastatic breast cancer
September 21, 2018 - CHMP grants positive opinion for VENCLYXTO plus rituximab for treating relapsed/refractory CLL
September 21, 2018 - Study offers solid link between visceral organs and brain’s reward, motivation system
September 21, 2018 - First U.S. patient treated with innovative gene therapy at Bascom Palmer Eye Institute
September 21, 2018 - New study shows how Ethiopia has managed to achieve extraordinary progress
September 21, 2018 - Choroidal Detachment – The American Society of Retina Specialists
September 21, 2018 - New clinical trial evaluates aesthetic results of conservative surgery in breast cancer
September 21, 2018 - Discovery of a key protein involved in the development of autism
September 21, 2018 - Air pollution appears to be linked to increased risk of developing dementia
September 21, 2018 - Henry Ford Health System receives $600k grant to study genetic makeup of gliomas
September 21, 2018 - Arthritis common in individuals with varying degrees of depression, finds study
September 21, 2018 - Scientist intends to fight pathogenic bacteria with viruses
September 21, 2018 - New research suggests link between PFAS chemicals and hyperthyroidism in pet cats
September 21, 2018 - Multi-year study data shows impact of new soft contact lens to slow myopia progression in children
September 21, 2018 - Neuroscientists identify circuit for brain’s statistical inference about motion
September 21, 2018 - MILabs’ VECTor6 system wins Commercial Innovation Award at WMIC 2018
September 21, 2018 - Scientists find wild African monkeys infected with bacterium that causes syphilis, yaws in humans
September 21, 2018 - 2006 to 2015 Saw Increase in Severe Maternal Morbidity
September 21, 2018 - Similar changes in the brains of patients with ADHD and emotional instability
September 21, 2018 - Cobalt mining in DR Congo takes a high toll on both creuseurs and environment
September 21, 2018 - Eating fatty fish during pregnancy may boost unborn child’s brain development
Harnessing Pediatric Cancer Genomic Data in the Cloud

Harnessing Pediatric Cancer Genomic Data in the Cloud

image_pdfDownload PDFimage_print

An interview with Dr. Jinghui Zhang, PhD, conducted by Kate Anderton, BSc

What is the history of genomics research at St. Jude Children’s Research Hospital?

In 2007, before the advent of next generation sequencing, St. Jude used microarrays to characterize gene expression and copy number variation and Sanger Sequencing to identify sequence mutations in leukemia. The experiments, led by Dr. Jim Downing and Dr. Charles Mulligan, were considered a major breakthrough at the time.

Image Credit: Mopic/ Shutterstock

In 2010, genome studies really started to take off around the world. St. Jude launched a USD $60 million project in collaboration with Washington University called the Pediatric Cancer Genome Project (PCGP) to investigate major pediatric cancers with very poor outcomes using whole genome sequencing.

At the time, only one human cancer genome had been sequenced using next-generation sequencing (NGS), and this was the AML genome. When we first started the project, the aim was to get Washington University to do the sequencing, as they were the ones who had sequenced the AML genome and thus, had the technology to carry out more analyses.

However, we now have a very integrative team who come from all areas of cancer research, from the clinical leads at St. Jude working on leukemia, solid tumors and brain tumors, to scientific leaders in these areas and computational biologists who work alongside them.

The big push at the moment is getting the Pediatric Cancer Genome Project completed. Phase I of the project, which focused on characterizing the genomic landscapes of major pediatric cancers, took three years to complete, from 2010-2013, then transitioned to a focus on germline predisposition analysis and epigenomic landscape between 2013-2015.

The project is now in its third phase, and the real clinical genomics efforts have begun. The first two years (2015-2017), involved a lot of planning and development of clinical sequencing infrastructure, and expansion of the germline research to include long-term survivors of pediatric cancer. We are now starting real-time clinical testing for every patient at St. Jude.

What is St. Jude Cloud and what does it provide to the global research community?

St. Jude research has generated significant data on pediatric cancer, and our CEO Dr. Downing and the institution as a whole are committed to sharing data with the broader research community. All PCGP data have been uploaded to public centralized repositories.

Image Credit: ImageFlow / Shutterstock

Scientists who want the data make a request, get approved, and download the data to their own local computing infrastructure. Data access has been granted to 300 research laboratories across the world.

What motivated us to develop St. Jude Cloud was the realization that downloading data from a public repository to a local computing infrastructure is a time-consuming process and only feasible for researchers with access to large computing infrastructure.

Hosting data on St. Jude Cloud will democratize data access and enable scientists to focus on carrying out innovative analysis instead of download data. Scientists can access data using our visualization tools and bring their own tools to the cloud to carry out innovative analysis.

What impact do you think St. Jude Cloud will have on patient care?

St. Jude Cloud attracts two main types of user. One is computer scientists and computational biologists who are interested in applying their innovative analysis tools to our data sets and using the data to make new discoveries. The other is translational scientists pursuing new treatments and diagnostic tests.

Our data sets cover the entire genome, so there are inevitably components of the genome that we haven’t explored in great detail yet. Someone with a particular research interest may use the data St. Jude has gathered as a starting point for a new research investigation.

Also, if another lab finds the same mutations as we do, they can combine their data with ours on St. Jude Cloud, which may provide sufficient statistical power by using the joint data. A statistically significant finding could guide the development of new treatments and diagnostic techniques.

My dream is that researchers will start to share data more routinely and the scientific community can work as a whole. As I said, pediatric cancer is a very rare disease, and if we don’t share data, it will be very difficult to move forward with treatment protocols and classify cancers in more detail for precision medicine.

Please describe your recent research in the field of pediatric cancer at St. Jude.

My most recent paper, published in Nature, focused on results of a pan-cancer analysis study, which was carried out in collaboration with the National Cancer Institute (NCI). We carried out genome-wide mutation signature analyses on almost 1,700 pediatric leukemias and solid tumors.

Before the study, we didn’t expect to see a striking pattern in terms of the mutation signatures, because unlike adults who get cancer, children are not exposed to many environmental risk factors for cancer, such as smoke or UV radiation. We therefore didn’t expect the environment to be a major contributor.

However, we were surprised to find a UV signature in eight aneuploid leukemias. We then wondered, is this observation real or is it just an incidental finding that is present to that group of patients from the Children’s Oncology Group that we sampled?

As we only have eight patients coming out of the study of about 300 cases, we will need to replicate the study in an independent cohort. However, Dr. Scott Newman, group lead for bioinformatics analysis at St. Jude who is leading the scientific aspect of St. Jude Cloud, explored whether we can use the data already in St. Jude Cloud to replicate the UV signature we found from the COG cohort.

We’re very satisfied to see that the UV signature was replicated. Furthermore, the replication was made in a cohort analyzed on a sequencing platform that is different from that used in the NCI study, further confirming that the pattern is not an artifact of sequencing.

Hence, we have now replicated the findings in two independent cohorts, using two different sequencing platforms, so we are very confident about the results. A study like that, typically, if you tried to download the data, would take at least a half year, minimum; whereas computing on St. Jude Cloud takes a fraction of that time to complete.

What technology did you use to carry out your research?

There are different aspects to the technology. We have our own local High-Performance Computing Cluster, but a cloud platform allows us to tab into even larger computing resources for managing intensive computing.

As St. Jude starts to use the results from clinical genomics for therapy, we need to complete data analysis in a fixed amount of time. Therefore, we need to overcome the computational bottleneck that holds us back at specific stages of data processing, and one of the ways this can be done is through cloud technology.

We are also starting to bring epigenetic profiling data sets into St. Jude Cloud. We think this will be very helpful in interpreting the regulatory variants in non-coding regions. These are areas of the human genome that have been rarely characterized, at present.

Another area is 3D genome architecture, looking at how different regions on the genome interact. This really helped us gain an insight into the regulatory variants that impact transcriptional networks in cancer.

Image Credit: klss / Shutterstock

How is technology changing the way that research is carried out at St. Jude and across the world?

Over the past decade, technology has become a lot more accessible. Take, for example, genome sequencing. In the past, only big genome centers could carry out sequencing analyses.

Now, using St. Jude Cloud, small labs can access huge datasets and computing power. If they send a specimen to a reference lab, they can check the quality of the data and ask questions about the validity of the results. I think, in a way, technology has democratized these genome-wide assays in a similar way to how Apple and Microsoft make computers accessible to the general public.

We are facilitating the ability of bench scientists to access complex data in a way that allows them to apply domain knowledge and their scientific insight to the data that is already out there. This allows us to connect the dots between computational scientists and bench scientists, who are currently considered to be two separate entities.

We hope that, with the increased accessibility of these assays and computing platforms, computational biology will become integrated and bench scientists can contribute to data analysis, even though they may not completely understand the computing technology behind it.

What does the future hold for your research team?

The pan-cancer study focused on the diagnosis of cancer, and relapsed cancers and how total evolution, from diagnosis to relapse, has not yet been fully elucidated.

What we’d like to do now is focus more on how tumors evolve in drug treatment. Hopefully, we can use this data to develop new cures for high-risk patients who relapse, because this is the bottleneck of treating pediatric cancer patients.

The second area that we’re working on is studying the general health of long-term survivors of pediatric cancer. This is part of an initiative called St. Jude LIFE, which is led by Dr. Les Robison at St Jude.

The St. Jude LIFE program longitudinally follows patients from St. Jude throughout their lifetimes to better understand the risks for side effects later in life. The goal is not just to cure patients with pediatric cancer, but also to ensure that they have a healthy and productive life.

We want to understand the long-term effects of cancer therapies, and whether it is possible to use genomics data to identify patients at high risk for late-stage toxic side effects. We hope that the findings can inform future research, so we can develop less toxic therapies that will improve the quality of life for kids in the future.

Finally, in our study, we only looked at the coding region of the genome, which equates to around 3 percent of the total genome. Now we need to look at the 97 percent non-coding DNA and identify variants.

This is more challenging than looking at coding mutations, because you need to understand the epigenetic landscape of pediatric cancer to be able to have a good interpretation of the non-coding variant that you’re looking at.

Where can readers find more information?

About Dr. Jinghui Zhang

Jinghui Zhang, PhD, is a computational biologist whose work focuses on the integrative analysis of large-scale, multi-dimensional genomics data to understand the initiation and progression of diseases.

In her early career, Dr. Zhang participated in the development of the widely used Basic Local Alignment Search Tool (BLAST) algorithm and led the genetic variation analysis of the first assembled human genome.

Dr. Zhang’s lab has developed innovative computational tools for analyzing and visualizing genetic variations and somatic mutations and has led the largest pediatric pan-cancer study in collaboration wtih the National Cancer Institute.

Dr. Zhang’s research group is primarily responsible for analyzing the whole-genome sequencing data generated from the St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project (PCGP).

Tagged with:

About author

Related Articles