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Genomics studies in neuroscience face a special challenge due to the brain’s complexity and scarcity of samples. Mapping changes in cell type and state using conventional next-generation sequencing methods remains challenging. Advances in technologies like single-cell sequencing, spatial transcriptomics, and long-read sequencing have opened the door to deeper studies of the brain and diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), and schizophrenia.
Probing disease mechanisms
“Single-cell and spatial technological advances have been critical for advancing brain science, whether for neurodegenerative disease, psychiatric disorders, or developmental neuroscience,” said Peter Smibert, VP of Biology at 10x Genomics. “Improvements in sequencing throughput and [multiplicity] of spatial assays have allowed scientists to generate population-level insights, building high-quality datasets powered by millions or billions of cells that can be used to train [artificial intelligence] models.” 10x has worked with multiple organizations including BioHub, Allen Institute, the Arc Institute, and others to build those datasets to enable target discovery for drug development.
10x single-cell sequencing technologies, including Chromium Flex Apex and GEM-X Universal, allow researchers to profile gene expression in individual cells, identify rare neural cell types and states, and uncover molecular mechanisms underlying neurological development and disease. “Our Flex Apex assay is ideal for large-scale scRNA-seq studies that aim to extract insights from datasets with millions, or even billions of cells,” Smibert added.
10x also supports spatial transcriptomic studies in neuroscience through its Xenium and Atera platforms. Xenium offers multiplex, in situ gene detection with subcellular resolution, and Atera, which launches in the second half of 2026, delivers whole-transcriptome spatial analysis with single-cell sensitivity. In a study published in Nature in 2024, researchers used Chromium technology to identify mechanisms of action behind Alzheimer’s disease and found a link between the APOE4/4 genotype and neurotoxic microglia-derived factors.
Long-read sequencing
PacBio provides systems for long-read sequencing, an approach that analyzes DNA or RNA segments up to tens of thousands of bases long, to customers in the life sciences. According to the company, its HiFi sequencing platform routinely produces read lengths of up to 25 kilobases with up to 99.5% accuracy. PacBio markets sequencing systems including its HiFi long-read platform and partners with research organizations to reveal disease mechanisms.
The firm in 2025 teamed up with Target ALS, a non-profit dedicated to accelerating ALS research, to sequence 6,000 genomes from around the world representing patients with ALS and healthy control subjects. The project’s goal is to find hard-to-detect genetic features that underlie the disease, such as structural variants and repeat expansions.
PacBio’s long-read capabilities are particularly important when studying repeat expansions, according to Elizabeth Tseng, Associate Director of Product Marketing at PacBio. For certain genes implicated in ALS, Tseng said it’s important to get an accurate read on repeat expansions because their length is a factor in predicting the risk of developing ALS and its progression. “Using PacBio you would be able to have a high-quality DNA characterization of the genomic regions of these repeat expansion disorders that are difficult to capture with other technologies,” Tseng explained.
PacBio’s approach can also offer advantages in RNA sequencing. “What’s hard about RNA sequencing in the human genome is that the same gene can produce multiple transcript isoforms through the process of alternative splicing,” Tseng said. “If you use short reads to sequence the same gene, you will not be able to definitely say this is the set of transcripts that were produced by this gene. With long reads, you can.”
Tseng said PacBio is a relative newcomer to the sequencing scene, and, as such, customers may not appreciate the advantages of long-read sequencing, especially when studying diseases like Alzheimer’s and Parkinson’s, which involve complex genomic and transcriptomic signatures. “When you see [the DNA] at the resolution we can with long reads, it makes a difference,” Tseng said.
A simpler single-cell workflow
Single-cell sequencing is changing how scientists study variation in gene expression across populations of cells and tissues. Parse Biosciences, an innovator in the development of single-cell sequencing technologies, offers a molecular bar coding and fixation workflow that allows customers to conduct single-cell sequencing using standard next-generation platforms.
Parse Biosciences Product Marketing Manager Karlie Fedder-Semmes said the company’s Evercode Whole Transcriptome (WT) product is particularly suited to neuroscience research. “[Evercode WT] gives us a really unbiased view of all cell types, cell states, and gene expression across complex samples,” Fedder-Semmes said, noting that Parse’s customers are choosing single-cell sequencing over bulk sequencing to get a clearer picture of disease biology in diseases like Alzheimer’s, ALS, and schizophrenia.
For example, in a study published in Nature Neuroscience in June, researchers with ETH Zurich and other institutions used Parse’s combinatorial barcoding to map regulatory mechanisms and cell composition in midbrain and hindbrain organoid models. In another collaboration, Parse is supporting the generation of a large, single-cell data set in Alzheimer’s and Parkinson’s disease with Mount Sinai researchers.
Fedder-Semmes said that Parse’s single-cell workflow is especially valuable in neuroscience, where human brain samples are scarce and very precious. “People are looking for technologies that can make the most out of the limited tissue they have,” she noted.
Because the technology is so new, Fedder-Semmes said researchers are often not aware of the possibilities it holds. “I really wish more researchers knew that they can think bigger about their single-cell study design,” she said. “We make those larger study designs come to life because we have an ability to match the scale of the experiment to the question the researcher is trying to answer.”
Catherine Shaffer holds a master’s degree in biological chemistry and has worked as a research scientist. She is also an award-winning science fiction author and part-time reporter for local public radio.