Axial: https://linktr.ee/axialxyz
Axial partners with great founders and inventors. We invest in early-stage life sciences companies such as Appia Bio, Seranova Bio, Delix Therapeutics, Simcha Therapeutics, among others often when they are no more than an idea. We are fanatical about helping the rare inventor who is compelled to build their own enduring business. If you or someone you know has a great idea or company in life sciences, Axial would be excited to get to know you and possibly invest in your vision and company . We are excited to be in business with you - email us at info@axialvc.com
Single-cell sequencing
Single-cell sequencing, led by tools developed by 10X Genomics and Akoya Biosciences, are enabling many new avenues in research and applications in drug development and diagnostics. Up to millions of cells can be manipulated and profiled to measure their heterogeneity and individual gene expression. The human genome has around 30K genes that produce over 100K mRNAs (splicing creates more variants). Each cell expresses around 10K genes with a few thousand having cell-specific patterns.
In 2003, the Human Genome Project was completed enabling new applications in particular genome-wide association studies (GWAS). The goal of this work was to build a database of genetic variants and link them to different phenotypes and disease. Due to the underlying complexity of biology, GWAS never fulfilled the promise of genomics. Large-scale sequencing efforts driven by the super-exponential decrease in costs and Illumina, helped increase access to data and scale up this work. The next step has been sequencing single cells to understand cell-to-cell variation, not just human-to-human, and their genomes, epigenomes, transcriptomes and proteomes. New tools are needed.
Beyond single-cell sequencing, we are also moving toward perturbing biological systems to measure changes within them. A catalog of genetic parts are being discovered, which is setting up for large-scale perturbation studies of single-cells. Coral Genomics is a leader here. This work could finally fulfill the original vision of the Human Genome Project: linking genetic variants to different traits and diseases.
What are some of the important problems to solve in single-cell sequencing?:
Integrate new single-cell measurements and standardizing them between samples: DNA, RNA, proteins, methylation, chromatin accessibility, spatial arrangement
Increasing sorting throughput/efficiency in single-cell sequencing. This would lead to large gains in resolution and the number of cells profiled. In some situations, due to these limitations only a few 100 cells can be measured. This would increase the number of cell types we discover along with their developmental trajectories.
Better analysis and visualization tools to analyze higher dimensional data. It seems there is a Something-seq paper every day, and this work has created a tremendous amount of data. Sometimes the data is pretty noisy due to low capture rates, batch effects, PCR biases, and more. Moreover, better tools to automate cell-type annotation are needed.
Single-cell sequencing is now building a parts list of individual cells. Whereas we had a parts list for individual humans but they did not fully recapitulate the complexity of biology. Single-cell probably doesn’t create a full picture by itself, but it is a major step forward in understanding biology and disease. For example, the human kidney, interactions between immune cells and antigens, tumor microenvironments, and more have been more accurately profiled because of these tools. With a better mechanistic understanding, we have a better shot at creating better medicines and products for human health.
In short, the main question in single-cell sequencing is - what does 10X or Akoya enable? 10X dominates the R&D part of the market and Akoya dominates clinical applications. Both companies are in an incredible market position and would be hard to usurp. As a result, new companies can think through new applications in oncology, autoimmunity, neurodegeneration, and more to build on top of. New immune cell profiling companies are springing up to find novel mechanisms to pursue in immuno-oncology and autoimmunity. 23andMe could even start integrating single-cell sequencing to their product line. New diagnostics can be created along with more accurate organoid models. Finding new insights from the spatial arrangements within cells is a new frontier. GWAS showed the power of new data helping generate better hypotheses. Single-cell sequencing is some orders of magnitude better in terms of scale and resolution. With this new data, inventors and founders should be able to ask better questions to understand biology and disease.