Single-Cell Long-Read Sequencing Service

Single-cell long-read sequencing is an advanced technology that combines single-cell resolution with long-read sequencing capabilities to analyze full-length RNA transcripts or DNA molecules. By capturing the complete structure of isoforms, including splicing events, transcription start sites, and polyadenylation sites, this method provides unprecedented insights into the molecular diversity of individual cells, enabling researchers to decode cellular identity and function with high precision.

 



Kumari, P. et al. Hum Genet. 2024.

Figure 1. The Workflow of Single-Cell Long-Read Sequencing

 

Single-cell long-read sequencing is conducted to overcome the limitations of short-read sequencing, such as the inability to resolve full-length transcripts or detect complex splicing patterns. This technology allows for detailed profiling of cell-type-specific isoforms, identification of structural variations, and discovery of novel transcripts, playing a crucial role in studying cellular heterogeneity, developmental processes, and disease mechanisms.

 

Services at MtoZ Biolabs

MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider, provides advanced proteomics, metabolomics, and biopharmaceutical analysis services to researchers in biochemistry, biotechnology, and biopharmaceutical fields. MtoZ Biolabs provides a single-cell long-read sequencing service utilizing advanced long-read technology to analyze full-length transcripts or genomes at the single-cell level. This service provides precise resolution of complex splicing patterns, transcription start sites, and polyadenylation sites, offering cell-type-specific insights. It supports research into cellular heterogeneity, functional differentiation, and disease-associated molecular features, delivering strong support for basic research and precision medicine.

 

Service Advantages

1. Comprehensive Analysis of Complex Splicing and Cell-Type-Specific Transcription  

MtoZ Biolabs’ single-cell long-read sequencing service accurately resolves RNA isoform splicing variations, providing detailed cell subtype-specific transcriptional insights. This technology reveals intricate cell-type-specific splicing patterns, advancing the understanding of cellular functions and molecular mechanisms.

 

2. High-Quality Genome Assembly and Structural Variant Detection  

With the power of Long-Read Sequencing, MtoZ Biolabs delivers high-quality genome assemblies and precise structural variant detection, including insertions, deletions, and rearrangements. This enables the analysis of complex regions and haplotype phasing with unparalleled accuracy.

 

3. Unveiling Cellular Complexity and Drug Development Targets  

Our single-cell long-read sequencing service explores the molecular basis of cellular complexity, excelling in identifying epigenetic modifications and resolving high-complexity genomic regions. These insights provide innovative pathways and targets for drug discovery and therapeutic research.

 

4. Integrated Multi-Omics Analysis with High Efficiency  

MtoZ Biolabs combines single-cell RNA transcriptomics, genomics, and epigenomics, offering a one-stop solution for multi-omics integration. Our optimized workflows address downstream challenges, providing efficient, precise, and actionable results for researchers.

 

Case Study

1. High Throughput Single Cell Long-Read Sequencing Analyses of Same-Cell Genotypes and Phenotypes in Human Tumors

The study introduces scNanoGPS, a novel tool for single-cell long-read sequencing that enables simultaneous analysis of single-cell genotypes (mutations) and phenotypes (gene/isoform expressions) without relying on short-reads or barcode guidance. Applied to 23,587 long-read transcriptomes, the research reveals distinct combinations of isoforms (DCIs) in tumors and stroma/immune cells, such as PDE10A in tumor cells and CCL3 in lymphocytes. Furthermore, transcriptome-wide mutation analyses identify cell-type-specific mutations, including VEGFA in tumor cells and HLA-A in immune cells, highlighting the critical roles of mutant populations in tumors. The single-cell long-read sequencing service enables simultaneous detection of isoform diversity and mutations across individual cells. By leveraging advanced long-read technologies, this service uncovers cell-type-specific molecular patterns and provides a comprehensive view of genotypes and transcriptomic phenotypes.

 



Shiau, CK. et al. Nat Commun. 2023.

Figure 2. Single Cell Long-Read Sequencing in Dissecting Cell Types in the Tumor Microenvironment

 

2. Single-cell Long-Read Sequencing-Based Mapping Reveals Specialized Splicing Patterns in Developing and Adult Mouse and Human Brain

Using single-cell long-read sequencing, this study analyzed the distribution and regulation of brain RNA isoforms across different regions, cell subtypes, developmental stages, and species. Full-length isoform expression of 72% of genes showed variability along one or more axes, with significant cell-type-specific regulation of splicing, transcription start sites, and polyadenylation sites, which are also associated with disease. The study found that developmental regulation of isoforms is stronger than regional regulation within the same cell type. While some mouse cell-type-specific isoform patterns are conserved in human brain tissues, additional cell-type-specific isoforms were identified in humans, suggesting the potential existence of gain-of-function isoforms. The single-cell long-read sequencing service enables precise characterization of isoform variability across developmental stages, anatomical regions, and cell types, uncovering unique splicing patterns and regulatory mechanisms in complex biological systems.

 



Joglekar, A. et al. Nat Neurosci. 2024.

Figure 3. Mapping Isoform Variability Across Region, Age, and Subtype in the Developing Mouse Brain

 

Deliverables

1. Comprehensive Experimental Details

2. Materials, Instruments, and Methods

3. Relevant Liquid Chromatography and Mass Spectrometry Parameters

4. The Detailed Information of Single-Cell Long-Read Sequencing

5. Mass Spectrometry Image

6. Raw Data