On July 12, 2023, in collaboration with the Center for Excellence in Brain Science and Intelligent Technology (Institute of Neuroscience) of the Chinese Academy of Sciences, BGI-Research, and other institutes, and international scientists from China and various other countries released the most comprehensive primate brain cell atlas to date. Their research paper was published in the journal Cell.

This groundbreaking discovery not only signifies a significant achievement for the global scientific community, providing a new foundation for research into brain diseases such as Alzheimer's and Parkinson's, but also for all of humanity, as it marks another significant stride in understanding ourselves. This achievement was made possible through the utilization of BGI's proprietary spatial-temporal omics technology, Stereo-seq, and the dedicated efforts of the scientists at BGI-Research. 

With the publication of this research today, key BGI researchers involved in this study shared the fascinating stories behind this pioneering research.

Q: Could you please elaborate on the challenges encountered during the research process and how the team addressed them?

Chen Ao: 

(Co-first author of the study, Chief Scientist of Spatio-Temporal Omics, Researcher at BGl-Research)

The first challenge we encountered was remotely deploying the technology. We arrived in Shanghai in 2020 to initiate this project. At that time, we were uncertain whether this novel technology could consistently yield stable and reliable data output in a completely new laboratory environment. However, after a week of training and testing, we achieved impeccable results. This marked the first successful deployment of Stereo-seq technology outside of a BGI laboratory.

The second challenge is the incredibly massive workload of mapping macaque brain cells, which necessitates a new collaborative approach that we refer to as the 'big science' paradigm. This paradigm enabled the team to work efficiently and at a fast pace, guided by a detail-oriented project management based on engineering principles.

For instance, during the brain mapping experimental phase, approximately 40 researchers from both BGI and the Center for Excellence in Brain Science and Intelligent Technology at the Chinese Academy of Sciences collaborated within the laboratory. The experimental plan was meticulously outlined down to every 15-minute interval, and astonishingly, the experimental phase was completed in just 6 days.

The success of this 'big science' paradigm has been evident, and we anticipate implementing it in numerous future projects.

Q: This research has generated 300TB of sequencing data, making it the largest data output in the field of the primate brain cell atlas to date. To address the challenges for algorithms, what efforts did the team undertake?

Li Yuxiang: 

(Co-corresponding author of the study, Chief Scientist of Bioinformatics, Researcher at BGl-Research)

This study stands at the forefront of the entire biology industry in terms of cell count, precision, and data size. During our initial project assessment, we conducted preliminary calculations for the overall experiment and analysis time based on the project design. We were shocked to find that the projected runtime for the project would exceed a year.

To tackle this issue, we quickly assembled our team of algorithm experts. After several days of discussions and late-night efforts, we successfully addressed the challenges of large-scale parallel processing by restructuring the overall framework and implementing improvements in various aspects, including data format, sequencing tags, and data integration.

As a result, we managed to condense the analysis time for data from a single sequencing chip to just one day, which previously would have taken over a month. In stress testing and final experiments, we completed data analysis in only 2 to 3 weeks, all thanks to the substantial optimizations implemented by a team that responded quickly and cooperated seamlessly.

Q: What significance does the primate cerebral cortex atlas generated by this study hold for advancing brain science?

Lei Ying: 

(Co-first author of the study, Director Scientist and Associate Researcher at BGI-Research) 

Utilizing BGI's proprietary Stereo-seq technology and high-throughput single-cell nuclear transcriptome sequencing technology, an international research team has successfully created the most comprehensive primate brain cell atlas to date.

This atlas carries significant implications for future functional analyses of the primate brain, as well as research on disease targets related to it and comparisons with other species throughout evolution. We hope that in the future, more global research teams can utilize this atlas to make further advancements in brain science and neuroscience research.

Q: In May 2022, an international scientific organization, the SpatioTemporal Omics Consortium (STOC) was established.What important progress has the STOC achieved since its establishment? What areas do you look forward to making more breakthroughs in the future?

Liu Longqi: 

(Co-corresponding author of the study, Chief Scientist of Single-cell Omics, Researcher at BGl-Research)

Since its establishment, the STOC consortium has attracted over 270 scientists from more than 35 countries to participate. Over the past year, the consortium has achieved remarkable progress and has published a series of notable accomplishments across various fields, including organ regeneration, embryonic development, neuroscience, and diseases, including the world's most comprehensive primate brain atlas presented this study.

Furthermore, considerable effort has been dedicated to organizing the consortium. For instance, we have formed the consortium's organizing committee, comprised of influential scientists from China and around the world in relevant fields. This committee plays a pivotal role in shaping the consortium's future development. It's responsible for making significant decisions regarding research directions and other crucial matters. 

Looking ahead, the consortium's primary research interests encompass the creation of spatial multi-omics cellular atlases for essential human organs, delving into fundamental questions in embryonic development, advancing the diagnosis and treatment of human diseases, and exploring the evolution of complex organ functions. The consortium is committed to expanding the application of spatio-temporal omics technologies across diverse domains, contributing to breakthroughs in scientific research.

Q: BGI has independently developed many advance technologies, leading global life sciences. What is behind such remarkable progress?

Xu Xun: 

(Co-corresponding author of the study, Director of BGI-Research)

Over the years, BGI has consistently adhered to a grand vision encapsulated as 'Omics for All.' 

To realize this vision, we are committed to gaining deeper insights into human diseases and the intricacies of human life. In response to these challenges, we have identified that single-cell technology and spatial-temporal omics technology, particularly the high-precision Stereo-seq technology, hold significant promise in unraveling the mysteries of life and diseases. Simultaneously, we encourage young talents to harness their creativity and ideas to propel technological innovations.

Guided by our overarching goal and bolstered by the innovative ideas of young talents within multidisciplinary teams, we persistently strive to achieve breakthroughs in cutting-edge technology.