September 11, 2019

Improving genomic data analysis – from soybeans to humans

By Colette Gallagher

Article by Colette Gallagher and Amy Clay-Moore

Daniel Wickland, Ph.D.

When Daniel Wickland, Ph.D., was a predoctoral student at the University of Illinois at Urbana-Champaign, he first worked to improve genomic data analysis for soybeans. But soon he shifted his focus, bringing his computer programming and informatics skills to work with Mayo Clinic and Illinois researchers to better understand Alzheimer’s disease as part of the Mayo Clinic and Illinois Alliance for Technology-Based Healthcare Research Fellowship program. Now he’s joined Mayo Clinic’s Department of Health Sciences Research, applying his skills to help better understand the underlying mechanisms driving breast cancer and to help develop immune-based cancer therapies.

Here’s a closer look at how Daniel’s research fellowship led him to his new role at Mayo Clinic.

A program to distinguish genomic differences  

During the first part of his graduate program, Daniel worked with Illinois crop sciences professor Matthew Hudson, Ph.D., to map a gene in soybeans that controlled plant height and internode length.

Early in the project, the team discovered the software they were using was not accurately identifying differences between soybean genomes. While seeking a solution, Wickland developed GB-eaSy, a program that dramatically increased the accuracy, speed, and simplicity of genotyping-by-sequencing data analysis.

When Hudson encountered a similar data analysis need in his research at the National Center for Super Computing Applications (NCSA), he immediately thought of Wickland’s work with soybean genomes.

“As a result of Dan’s prior work on variant calling software, and his interest in neuroscience from his undergraduate days in the Illinois Neuroscience Program, I thought he would be an excellent candidate for the Alzheimer’s disease sequencing project,” says Hudson. “Although soybeans and humans are very different, the bioinformatics problems involved were closely related,” says Hudson.

Hudson’s work with Liudmila Mainzer, Ph.D., senior research scientist at NCSA, and Yan Asmann, Ph.D., associate professor of biomedical informatics at Mayo, focused on improving genetic variant calling software for human genomics targeted at Alzheimer’s disease.

The collaborators used Blue Waters, NCSA’s petascale computer, to perform a vast number of comparisons to troubleshoot the huge amount of genome data that Mayo was analyzing on Alzheimer’s disease.

Although Wickland was nearing completion of his doctoral degree in crop sciences, he decided to transfer to the Informatics Ph.D. program and join this new project to focus on bioinformatics.

In the first year of his fellowship at NCSA, Wickland developed skills in high-performance computing and workflow programming. He mastered the complex workflows on Blue Waters necessary to analyze the data in several ways to determine the source of inconsistencies they were finding.

Over two years, the project used more than 600,000 node hours on Blue Waters, which is equivalent to a single server running continuously for almost 100 years.

“These intensive computing needs could not have been met without a resource like Blue Waters at NCSA” says Wickland. “Also critical to the success of this project were feedback and ideas from Dr. Hudson and Dr. Mainzer, my advisors at NCSA.”

Collaborating with Mayo Clinic experts to refine data analysis

In his second year, Wickland worked at the Mayo Clinic campus in Florida and with Illinois researchers to analyze genomic sequencing data of more than 10,000 cases and healthy controls from the project.

“I received invaluable guidance from my Mayo advisor, Dr. Asmann, and very helpful feedback from renowned Alzheimer’s researchers at Mayo,” notes Wickland. “Working in these two environments – Mayo Clinic and NCSA – exposed me to different methods and ideas that strengthened my skills as a researcher.”

“He was ultimately able to determine that in this case, the problem did not lie in the software itself, but in the discrepancies between the data generated at the different participating institutions in the project,” says Hudson.

A new role

After receiving his doctoral degree, Wickland joined the Mayo Clinic Department of Health Sciences Research. He is working on a project that focuses on breast cancer immunogenomics with Dr. Asmann, Keith Knutson, Ph.D., professor of immunology, and Mark Sherman, M.D., professor of epidemiology and laboratory medicine and pathology.  

“I’m currently studying how the immune system responds to tumor neoantigens (protein fragments found only on the surface of cancer cells), how this response differs among individuals and among racial groups, and how we can use this information to predict and enhance the anti-tumor immune response in a personalized manner. This genomics research will support efforts in the Center for Individualized Medicine to develop customized cancer vaccines targeted to the specific neoantigens produced by a patient’s tumor,” says Dr. Wickland.

The Mayo-Illinois Alliance for Technology-Based Healthcare was founded in 2010 by Mayo Clinic and the University of Illinois – Urbana Champaign to advance research and clinical treatment options related to individualized medicine.

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Tags: #Dr. Daniel Wickland, #Dr. Keith Knutson, #Dr. Liudmila Mainzer, #Dr. Matthew Hudson, #Dr. Yan Asmann, Alzheimer’s disease, Bioinformatics, Cancer, center for individualized medicine, crop science, Genomic Sequencing, genomics, immunology, mayo clinic, Mayo Clinic Department of Health Science Research, Mayo-Illinois Alliance for Technology-Based Healthcare, medical research, National Center for Super Computing Application, Precision Medicine, Research, University of Illinois – Urbana Champaign

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