Lopez laboratory develops computer tools to better understand complex biological systems | News

By Aaron Conley

Systems Biology and Lopez Laboratory

The history of hermeneutics began with Aristotle – the parts make up the whole. To understand the whole, you have to understand the parts. And to understand the parts, we have to understand them in the context of the whole.

Carlos F. Lopez, associate professor of biochemistry, described this concept and its connection to systems biology. The field of biomedical research has “spent a lot of time breaking the whole thing down to understanding the individual components, such as organs in a human or individual cells in a tissue,” Lopez said. “But now we’re trying to take our knowledge of the components and understand how each works as part of the whole system.”

Biological researchers are now at a point where instrumentation, large genotyped and phenotyped datasets, and computational analysis can be used to address complex systems biology questions in the search for new discoveries. Lopez’s lab uses these tools, including computational modeling, machine learning, and dynamic network analysis methods, to explain and predict cellular behaviors, with a focus on dysregulating mechanisms, like the one found in cancer. The lab also creates tools that can aid in systems biology research. The Lopez Lab has had a prolific year, publishing six papers in 2021 and developing several open source tools.

Lopez’s draw on the pitch

Lopez was drawn to huge scientific questions that require multiple perspectives to find the answer. For example: when you have a headache, you take a pill, then it enters your bloodstream and your organs, and it blocks a molecule to eliminate your headache. “But how,” Lopez asked, “molecular interactions that take place on the scale of nanoscale space and on the femtosecond time scale translate into a whole-body response? A femtosecond is a second , like a second is a century. That’s like trying to figure out how this interview is going to change the whole earth in 100 years! Understanding how molecular changes alter the whole body is a very difficult problem because small things can have huge impacts, and we don’t yet know how it works – mutations, viruses, drugs, etc. – these happen on a small scale but have huge impacts.”

Unpacking these systems biology questions requires massive amounts of (often) noisy or uninformative data. “Nature has evolved despite the noise of this data,” Lopez explained. “This is a fundamental question that we want to answer: how does nature work?

To get those answers, “we can generate a lot of data,” Lopez said. “Our mass spectrometry cores can measure 100,000 proteins and metabolites at one time, at any given time, and we need tens or even hundreds of time points to extract mechanistic insights from this data. So we get into the millions of steps very quickly. Additionally, scRNA-seq data provides gene expression information for thousands of cells, each comprising approximately 20,000 genes, at any given time. You quickly access millions and billions of data points. These are terabytes of data. It’s very complex to understand, to derive knowledge from so many measurements, and that’s our challenge: how to take this data and turn it into knowledge? »

Tool development

Often the tools to address these challenges simply do not exist, which is why the Lopez lab will develop them. One of these tools, recently developed by the Lopez laboratory and its collaborators, is Thunor, which organizes, analyzes and visualizes cellular responses to drug treatment using high-throughput screening. The ability to visualize and analyze cell proliferation has significant implications for drug discovery efforts. Lopez’s goal with Thunor is to have “open source tools to make crowd-based knowledge accessible and move the field forward.”

In collaboration, Lopez and Vito Quaranta, professor of biochemistry and director of the Vanderbilt Quantitative Systems Biology Center, have developed a new theory and algorithm called MuSyC to deconvolute drug combination efficacy and potency in cancer. David Wooten, PhD’18, and Christian Meyer, PhD’20, who both have a background in physics, developed the MuSyC theory, published in the journal Nature Communication, and presented its application in a separate publication in Cellular systems. Lopez explained that MuSyC has the “potential to transform the business of drug combination displays.” MuSyC works by precisely guiding researchers and doctors to drug combinations they can prescribe to patients at lower doses, with improved efficacy, or both. Learn more about MuSyC here.

The Lopez Lab’s software, tools, and expertise help international researchers sift through big data to derive hypotheses through analyzes that help reduce bias and open up new discoveries. Lopez added, “Systems biology is at a threshold where something big is going to happen.”

Go further – Lopez laboratory publications

Funding

The above research was supported by the Vanderbilt International Students Program, National Science Foundation, National Institutes of Health, National Cancer Institute, National Library of Medicine, Vanderbilt Biomedical Informatics Training Program, and Defense Advanced Research Projects Agency .

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