Building a neuronal atlas with single-cell technologies

Dr. Lynette Lim leads the Laboratory of Interneuron Developmental Dynamics at the Center for Brain and Disease, part of the Flemish Center for Biotechnology (Vlaams Instituut voor Biotechnologie, VIB). The group explores how the diversity of neuronal cell types emerges in the brain, leveraging the latest advancements in single-cell technology and Genevia Technologies’ support in data analysis.

Dr. Lim with her lab

Navigating neuronal diversity

Dr. Lim characterizes her group as a traditional neurodevelopmental laboratory, dedicated to studying the diversity of cell types in the mammalian brain and understanding the molecular mechanisms that drive their maturation and specification. However, like many others in the field, her team has witnessed the transformative shift brought about by single-cell technologies. Dr. Lim explains that single-cell technology enables the tracking of cells throughout their developmental stages, providing insights into the activation and deactivation of genetic programs specific to each cell type, which could not be achieved by classical tissue sampling approaches. Consequently, the group has redirected their focus from the most stereotypical cell types to extremely rare ones. Dr. Lim states their objective as building what she calls a neuronal atlas.

– With single-cell technology, we have collectively, as a field, built something akin to the first version of a world atlas. We have a rough idea of the continents, but precision is lacking. What we are aiming to construct is more like a detailed map of London, depicting every street, turn and corner, specific to London alone, she explains.

The cells of interest, though scarcely encountered, play pivotal roles in the cerebral cortex, the outer layer of the brain. Dr. Lim’s initial idea was to gather publicly available data to trace the developmental trajectory of these cell types. However, this proved unexpectedly challenging: the quality of the public data sets fell short of their expectations, not allowing everything to be linked together. In the meantime, while compiling the public data, the team conducted numerous high-depth single-cell RNA-Seq experiments. Now, the revised plan is to build a scaled-down version of the atlas using this high-resolution, cell-specific data. Moreover, they intend to incorporate ATAC-Seq to gain further insights into these cells.

Dr. Lim had noticed Genevia Technologies acknowledged in several publications, and when the need for bioinformatics support became topical in her group, she reached out to the company to learn whether they could assist in her research as well.

– While we do have considerable in-house bioinformatics support within our center, it mostly caters to routine bioinformatics tasks, such as data matrix preparation, genome alignment, and generating standard plots. Rather than this kind of classical bioinformatics, this one-of-a-kind project required specialized expertise.

Collaboration with Genevia Technologies

In initial discussions with the Genevia team, Dr. Lim was pleased to find out that they offered a month-to-month contract, allowing for a trial period before committing to outsourcing their bioinformatics. The trial proved successful, resulting in a nine-month contract that was recently extended for another year. Dr. Lim summarizes her experience with Genevia in one word:

– The keyword here is collaboration. Typically, when contracting a service, you specify what you want, and the next interaction occurs months later when the service provider delivers the final product. With Genevia, it’s different: this project on such unexplored territory is an ongoing iteration. We hold regular meetings every couple of weeks, which enables us to readjust the baseline based on the information from the previous analyses. So even though we are paying a fee, I view it more as a collaborative effort rather than a conventional fee-for-service system.

Dr. Lim highlights that Genevia’s service is well-suited to academic research. Her group is relatively small and primarily engaged in experimental work. Every now and then, they receive large batches of data that require analysis, but the primary focus of the individuals in the group is to develop their skills in the physical lab rather than learning data analysis. Hiring a bioinformatician doesn’t seem like a practical solution either:

– If we were to hire a full-time bioinformatician, that person would not necessarily have a lot to do, and, in addition, that person would probably have their own career goals in academia, meaning that they would need a bioinformatics-based project of their own. It would not be possible for them to do someone else’s project in this kind of 0.25 full time equivalent arrangement, for example. That’s why Genevia’s setup itself is very good, and I guess I’ve also been lucky in terms of the bioinformatician I’ve got to work with, she notes.

Dr. Lim says that she already knows a couple of colleagues that have reached out to Genevia based on her recommendation, and encourages people to explore the option. She’s looking forward to continuing the collaboration and building the neuronal atlas together with the Genevia team:

– Overall, I have been very happy so far. We’re not in the full delivery state yet, but things are moving along well and we’ve got some promising results.

See the first publication from this work: https://doi.org/10.1016/j.neuron.2023.11.013