Studying Neural Circuit Development With Single-Cell RNA-Sequencing

The Laboratory for Cell Fate Specification and Circuit Development at the Burke Neurological Institute, Weill Cornell Medical College, studies mechanisms of neural circuit development with the aim to apply that knowledge to regenerate circuits in instances of disease and injury. We interviewed the lab director, Dr. Vibhu Sahni, who contracted Genevia Technologies to support their research with single-cell RNA-seq data analysis.

Sahni lab

Advancing neural circuit research with bioinformatics

Dr. Vibhu Sahni is an Assistant Professor at the Weill Cornell Medical College, and leads the Laboratory for Cell Fate Specification and Circuit Development at the Burke Neurological Institute. With a strong background in regenerative neuroscience, his research is now focused on movement-controlling neural circuits, specifically corticospinal circuitry development, repair and plasticity.

In the summer of 2023, aiming to identify new genes and molecules that control the development of targeted neural circuits, the group performed single-cell RNA-sequencing. In separate lines of experiments, the lab had previously applied single-cell and bulk transcriptomics, as well as microarrays, and had a collaborator handle the data analysis. However, there was now a need for more advanced analysis and assistance in interpreting the data. The solution was found through a friend:

– I heard about Genevia completely by referral: my friend and colleague, Dr. Lynette Lim, who has a lab in Leuven, Belgium, put me in touch with her bioinformatician at Genevia with whom she had been working, explains Dr. Sahni.

Help from a dedicated bioinformatics expert

Faced with a project whose bioinformatics needs he describes as anything but straightforward, Dr. Sahni decided to contract Genevia’s support. Outsourcing the data analysis proved to be the right choice. Practicalities to kick off the project, as well as communication between the Sahni lab and the Genevia team throughout the project, worked seamlessly. Dr. Sahni explains the background behind the decision:

– No one else has done what we are trying to do. I can find papers in which something similar has been done, but whether or not it’s perfectly applicable for our work – I can’t be the best judge of that because I don’t speak the bioinformatic lingo. It is a huge advantage to have someone who is an expert in the field to help you, he says, and continues to praise the bioinformatician they worked with:

– I really appreciate the way he took it upon himself to take the lead. For our analysis, everything had to be custom-tailored. Whenever I asked him to check out the papers I had found and see if their methods could be applied to our project, the next time we met, he could already explain how everything worked and what were the pros and cons of the approach. And when we, in turn, explained our field to him, he understood it immediately, and that overlap grew stronger throughout the project.

Dr. Sahni gives an example of such a situation that impressed him: he had found an analysis pipeline and talked to the researchers who had built it, interested in applying the tool. However, it did not seem to pan out with his single-cell data from the cortex, until he explained the situation to Genevia's bioinformatician, who swiftly spotted the problem.

Reflecting on the advantages of outsourcing bioinformatics, Dr. Sahni notes that the common solution, an academic collaboration, suffers from limited time: the collaborators have their own projects, too. Through Genevia’s Virtual Bioinformatics Core, he got a bioinformatician fully dedicated to his project.

After the data analysis wrapped up, the Sahni lab has started to prepare a manuscript to publish their intriguing and unexpected results. He says that he hopes to continue the great interaction with Genevia:

– I don’t think we could have done what we have without the assistance of Genevia; the results are, without a doubt, better off for it. I think their service definitely was an asset, and I highly recommend it: every time I give a talk somewhere, and get questions regarding this approach, I talk about Genevia.

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