soybeans

Drowning in Data

New web-based framework helps scientists analyze and integrate data

By Emily Kummerfeld | Bond LSC

Large-scale data analysis on computers is not exactly what comes to mind when thinking about biological research.

But these days, the potential benefit of work done in the lab or the field depends on them. That’s because often research doesn’t focus on a single biological process, but must be viewed within the context of other processes.

Known as multi-omics, this particular field of study seeks to draw a clearer picture of dynamic biological interactions from gigantic amounts of data. But, how exactly can scientists suitably weave multiple streams of information together, especially considering technology limits and other biological variables?

Trupti Joshi and her team are seeking to find a solution to that problem.

Joshi, as part of the Interdisciplinary Plant Group faculty, works on translational bioinformatics to develop a web-based framework that can analyze large multi-omics data sets, appropriately entitled “Knowledge Base Commons” or KBCommons for short. She describes KBCommons as “a universal, comprehensive web resource for studying everything from genomics data including gene and protein expression, all the way to metabolites and phenotypes.”

Her work began about eight years ago with soybeans. Dubbed the Soybean Knowledge Base (SoyKB), her team had developed a lot of their own data analysis tools for soybean research, but they realized the same tools could help research of other organisms. From there sprouted the Knowledge Base Commons, intended for looking at plants, animals, crops or disease datasets without the need to “reinvent the wheel” each time.

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Soybean plants used in research that utilizes Soy KB web-based network. | Emily Kummerfeld, Bond LSC

“Our main focus has been in enabling translational genomics research and applications from a biological user’s perspective, and so our development has been providing graphic visualization tools,” Joshi said.

Those tools provide an array of colorful graphics from basic bar graphs to assorted colored pie charts to help the researcher better analyze the data once data has been added to the KBCommons.

Colorful graphs and comparisons lets many researchers look past the lines of text and tables full of numbers that represent genes, plant traits or other experimental results, and making the interpretation of data much more easier and efficient.

One particular tool allows the researcher to look at the differential genes of four different comparisons or samples at the same time. Differential genes are the genes in a cell responding differently between different experimental conditions. For example, a blood cell and a skin cell both have the same DNA, however, some genes are not expressed in the blood cell that are expressed in the skin cell. With this KBCommons tool, a researcher can examine genes to see “what are the common ones, what are the unique ones to that, and at the same time look at the list of the genes and their functions directly on the website, without having to really go and pull these from different websites or be working with Excel sheets,” Joshi explained.

She envisions KBCommons as a tool to enable translational research as well. Users will be able to compare crops, such as legumes and maize for food security studies, or link research between veterinary medicine and human clinical studies for better therapies.

Intended for a wide range of users, Joshi is keenly aware of its potential users right here at MU.

One current user of the Soybean Knowledge Base (SoyKB) system is Gary Stacey, whose lab at Bond Life Sciences Center studies soybean genomics and to date has been the longest user of the SoyKB resource. Like many researchers, Stacey explained the need for a program like SoyKB that can process enormous amounts of data.

“The reason it’s called “Knowledge Base” is the idea that we’re putting information in, and what we hope to get out is knowledge. Because information is different than knowledge,” he said, “we don’t just want to collect stamps, we want to be able to actually make some sense out of it…By having a place to store the data, and then more importantly have a place to analyze it and integrate it, it allows us to ask better questions.”

This is essential, given that one soybean genome is 1.15 GB in size, and one thousand soybean genome sequences could generate 30 to 50 TB of raw sequencing data and tens of millions of genomic variations (SNPs).

But such numbers are modest compared to the program’s true capabilities.

“The KBCommons system is so powerful that it can allow you to run thousands of genomes at the same time using our XSEDE gateway allocations,” Joshi said. “This whole scalability is a unique feature of KBCommons, which a lot of databases do not provide, and we are happy we have been able to bring that to our MU Faculty collaborators on these projects, so that they can really utilize the remote high performance computing (HPC), cloud storage and new evolving techniques in the field.”

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KB Commons is a new web-based network for biological data analysis and integration developed by students. | Emily Kummerfeld, Bond LSC

Mass data capability and colorful graphs aside, her favorite part is who exactly is designing the program.

“What I like most about KBCommons is that it serves as a training and development ground and is developed by students, undergraduate and graduate students from computer science and our MUII informatics program.”

KBCommons is still under development, but publication and access for all users is planned for the end of this year or early 2018. Users will not only be able to view public data sets, but add their own private data sets and establish collaborative groups to share data.

Dr. Trupti Joshi is an Assistant Professor and faculty in the Department of Health Management Informatics, the Director for Translational Bioinformatics with the School of Medicine, and Core Faculty of the MU Informatics Institute and Department of Computer Science and the Interdisciplinary Plant Group.

 

Chemical persuasion

Scientists prove parasite mimics key plant peptide to feed off roots
By Roger Meissen | Bond LSC

A nematode (the oblong object on the upper left) activates the vascular stem cell pathway in the developing nematode feeding site (syncytium) on a plant root. | contributed by Melissa Mitchum

A nematode (the oblong object on the left) activates the vascular stem cell pathway in the developing nematode feeding site (syncytium) on a plant root. | photo by Xiaoli Guo, MU post-doctoral research associate

When it comes to nematodes, unraveling the root of the issue is complicated.

These tiny parasites siphon off the nutrients from the roots of important crops like soybeans, and scientists keep uncovering more about how they accomplish this task.

Research from the lab of Bond LSC’s Melissa Mitchum recently pinpointed a new way nematodes take over root cells.

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Melissa Mitchum | photo by Roger Meissen, Bond LSC

“In a normal plant, the plant sends different chemical signals to form different types of structures for a plant. One of those structures is the xylem for nutrient flow,” said Mitchum, an associate professor in the Division of Plant Sciences at MU. “Plant researchers discovered a peptide signal for vascular stem cells several years ago, but this is the first time anyone has proven that a nematode is also secreting chemical mimics to keep these stem cells from changing into the plant structures they normally would.”

Stem cells? Xylem? Chemical mimics?

Let’s unpack what’s going on.

First, all plants contain stem cells. These are cells with unbridled potential and are at the growth centers in a plant. Think the tips of shoots and roots. With the right urging, plant stem cells can turn into many different types of cells.

That influence often comes in the form of chemicals. These chemicals are typically made inside the plant and when stem cells are exposed to them at the right time, they turn certain genes either on or off that in turn start a transformation of these cells into more specialized organs.

Want a leaf? Expose a stem cell to a particular combination of chemicals. Need a root? Flood it with a different concoction of peptides. The xylem — the dead cells that pipe water and nutrients up and down the plant — requires a particular type of peptide that connects with just the right receptor to start the process.

But for a nematode, the plan is to hijack the plant’s plan and make plant cells feed it. This microscopic worm attaches itself to a root and uses a needle-like mouthpiece to inject spit into a single root cell. That spit contains chemical signals of its own engineered to look like plant signals. In this case, these chemicals — B-type CLE peptides — and their purpose are just being discovered by Mitchum’s lab.

“Now a nematode doesn’t want to turn its feeding site into xylem because these are dead cells it can’t use, so they may be tapping into part of the pathway required to maintain the stems cells while suppressing xylem differentiation to form a structure that serves as a nutrient sink,” Mitchum said. “To me that’s really cool.”

This means these cells are free to serve the nematode. Many of their cell walls dissolve to create a large nutrient storage container for the nematode and some create finger-like cell wall ingrowths that increase the take up of food being piped through the roots. For a nematode, that’s a lifetime of meals for it while it sits immobile, just eating.

But how did scientists figure out and test that this nematode’s chemical was the cause?

Using next generation sequencing technologies that were previously unavailable, Michael Gardner, a graduate research assistant, and Jianying Wang, a senior research associate in Mitchum’s lab, compared the pieces of the plant and nematode genome and found nearly identical peptides in both — B-type CLE peptides.

“Everything is faster, more sensitive and we can detect things that had gone undetected through these technological advances that didn’t exist 10 years ago,” Mitchum said.

To test their theory, Xiaoli Guo, postdoctoral researcher and first author of the study in Mitchum’s lab synthesized the B-type CLE nematode peptide and applied it to vascular stem cells of the model plant Arabidopsis. They found that the nematode peptides triggered a growth response in much the same way as the plants own peptides affected development.

They used mutant Arabidopsis plants engineered to not be affected as much by this peptide to confirm their findings.

“We knocked out genes in the plant to turn off this pathway, and that caused the nematode’s feeding cell to be compromised. That’s why you see reduced development of the nematode on the plants.”

This all matters because these tiny nematodes cost U.S. farmers billions every year in lost yields from soybeans, and similar nematodes affect sugar beets, potatoes, corn and other crops.

While this discovery is just a piece of a puzzle, these pieces hopefully will come together to build better crops.

“You have to know what is happening before you can intervene,” Mitchum said. “Now our biggest hurdle is to figure out how to not compromise plant growth while blocking only the nematode’s version of this peptide.”

Mitchum is a Bond LSC investigator and an associate professor of Plant Sciences in the College of Agriculture, Food and Natural Resources. The study Identification of cyst nematode B-type CLE peptides and modulation of the vascular stem cell pathway for feeding cell formation” recently was published by the journal PLOS Pathogens in February 2017.