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###### ResolveDNA Whole Genome Amplification Kits overcome the inherent challenges of low coverage uniformity in single-cell genomics that lead to increased sequencing costs and complex data analysis.

The controlled reaction parameters employed in this PTA-based kit enables reproducible recovery of >95% of the genomes of single cells and limited DNA input samples with industry-leading uniformity and accuracy.

Key features and benefits of ResolveDNA Whole Genome Amplification Kits include:
- Complete genomic coverage with bulk sample quality from a single cell
- Significantly lower allelic dropout and biases compared to existing WGA methods that yield low and variable coverage across the genome
- Specific amplification of the primary template with >97% of reads mapping to the human genome
- Low-cost, scalable approach to WGA with up to 384 reactions per kit
- Simple, user-friendly workflow that requires less than 30 mins of hands-on time and can be set up with automation

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**Designed for Ease of Use**
- Simple, user-friendly workflow that requires less than 30 mins of hands-on time for cell lysis and WGA
- An 8-hr, starting material to NGS run workflow
- Optimized for both automated and manual reaction set-up

###### ResolveDNA Whole Genome Amplification Kits offer superior coverage and uniformity in single-cell WGS. 

Ten single cells were isolated from a human B-lymphocyte cell culture (CEPH1463/NA12878/ GM12878 human genome reference standard). WGA was performed on individual cells, using the ResolveDNA Whole Genome Amplification Kit. WGA products were converted to indexed libraries and subjected to high-coverage whole genome sequencing (WGS) on the Illumina® platform. For the other WGA methods, low-pass WGS data (generated from individual BJ1 fibroblasts), were obtained from a previously published study (Chen, C. et al. Science 2017; 356: 189).

To achieve a fair comparison of the various WGA methods, raw data for all samples were aligned and pre-processed for variant calling using the same pipeline. All metrics shown in the table were generated from randomly subsampled BAM files (300 million reads per cell). Note that the metrics for all the methods other than the ResolveDNA kit are overestimates, due to the way in which data analysis was performed in the original study. ResolveDNA metrics were generated using the first version of the ResolveDNA Whole Genome Amplification Kit. The newer ResolveDNA Whole Genome Single-Cell Core Kit achieves similar metrics with a noted increase of SNV sensitivity to 96%

[new:MSDS](https://static.bioskryb.com/uploads/Resolve_DNA_Whole_Genome_Amplification_Kit_MSDS_e3ff3b69fd.zip)

[new:MSDS (ResolveDNA V2)](https://static.bioskryb.com/uploads/Bio_Skryb_Resolve_DNA_Whole_Genome_Amplification_Kit_v2_0_SDS_Sheets_v2_5c78fac3a5.zip)

ResolveDNA® Product Brochure

Accurate Genomic Variant Detection in Single Cells with Primary Template-Directed Amplification

Ultraspecific somatic SNV and indel detection in single neurons using primary template-directed amplification

Dementia in Alzheimer’s disease progresses alongside neurodegeneration1–4, but the specific events that cause neuronal dysfunction and death remain poorly understood. During normal ageing, neurons progressively accumulate somatic mutations5 at rates similar to those of dividing cells6,7 which suggests that genetic factors, environmental exposures or disease states might influence this accumulation5. Here we analysed single-cell whole-genome sequencing data from 319 neurons from the prefrontal cortex and hippocampus of individuals with Alzheimer’s disease and neurotypical control individuals. We found that somatic DNA alterations increase in individuals with Alzheimer’s disease, with distinct molecular patterns. Normal neurons accumulate mutations primarily in an age-related pattern (signature A), which closely resembles ‘clock-like’ mutational signatures that have been previously described in healthy and cancerous cells6–10. In neurons affected by Alzheimer’s disease, additional DNA alterations are driven by distinct processes (signature C) that highlight C>A and other specific nucleotide changes. These changes potentially implicate nucleotide oxidation4,11, which we show is increased in Alzheimer’s-disease-affected neurons in situ. Expressed genes exhibit signature-specific damage, and mutations show a transcriptional strand bias, which suggests that transcription-coupled nucleotide excision repair has a role in the generation of mutations. The alterations in Alzheimer’s disease affect coding exons and are predicted to create dysfunctional genetic knockout cells and proteostatic stress. Our results suggest that known pathogenic mechanisms in Alzheimer’s disease may lead to genomic damage to neurons that can progressively impair function. The aberrant accumulation of DNA alterations in neurodegeneration provides insight into the cascade of molecular and cellular events that occurs in the development of Alzheimer’s disease.

Here we analysed single-cell whole-genome sequencing data from 319 neurons from the prefrontal cortex and hippocampus of individuals with Alzheimer’s disease and neurotypical control individuals.

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Somatic genomic changes in single Alzheimer’s disease neurons

ResolveDNA® in primary breast cancer

Distinct resistance modalities to targeted kinase inhibition exposed by single-cell Primary Template-directed Amplification in acute myeloid leukemia and triple-negative breast cancer.

Accurate detection of small genomic variants, copy number alterations, and heteroplasmy in early human embryos.

Improving the sensitivity of detection of low frequency somatic variants via Primary Template-directed Amplification of single cells.

Accurate Single-cell Genomic Analysis Holds the Key to Understanding Cancer Heterogeneity

ResolveDNA® Lysis Optimization

ResolveDNA® Interactive Tech Note

Genome-Wide Disease Screening in Early Human Embryos with Primary Template-Directed Amplification

Validation of the first PGT-whole genome sequencing approach including mitochondrial variants

Realtime morphological characterization and sorting of unlabeled viable cells using deep learning

Somatic mutations reveal hypermutable brains and are associated with neuropsychiatric disorders

Artificial intelligence-driven morphology-based enrichment of malignant cells from body fluid

Comprehensive single-cell genome analysis at nucleotide resolution using the PTA Analysis Toolbox

Contrasting patterns of somatic mutations in neurons and glia reveal differential predisposition to disease in the aging human brain

Defining ancestry, heritability and plasticity of 2 cellular phenotypes in somatic evolution

High-Quality Nuclei Isolation from Postmortem Human Heart Muscle Tissues for Single-Cell Studies

Co-culture of intestinal organoids with a colibactin-producing pks+ E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E. coli Nissle 1917 (EcN) remains a commonly used probiotic, despite harboring the pks operon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+ E. coli strains with an analytical framework based on sequence characteristic of colibactin-induced mutations. All strains, including EcN, display varying levels of mutagenic activity. Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ~12% of CRCgenomesandevenin whole exome sequencing data, representing a crucial step toward pinpointing the mutagenic activity of distinct pks+ E. coli strains.

We determine the mutagenicity of EcN and three CRC-derived pks+ E. coli strains with an analytical framework based on sequence characteristic of colibactin-induced mutations.

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Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer

We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of brains harbored hundreds of somatic mutations. Hypermutability was associated with age and damaging mutations in genes implicated in cancers and, in some brains, reflected in vivo clonal expansions. Somatic duplications, likely arising during development, were found in ~5% of normal and diseased brains, reflecting background mutagenesis. Brains with autism were associated with mutations creating putative transcription factor binding motifs in enhancer-like regions in the developing brain. The top-ranked affected motifs corresponded to MEIS (myeloid ectopic viral integration site) transcription factors, suggesting a potential link between their involvement in gene regulation and autism.

Our study revealed a complex etiology of somatic mutations in brain and their possible relationship with phenotype.

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Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability

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ResolveDNA® scDNAseq
Single-Cell DNA Sequencing Kits

Unlock the entire genome and enhance the discovery
potential of your single-cell genomics with ResolveDNA.
See what you have been missing

ResolveDNA Whole Genome Amplification Kits overcome the inherent challenges of low coverage uniformity in single-cell genomics that lead to increased sequencing costs and complex data analysis.

ResolveDNA Whole Genome Amplification Kits offer superior coverage and uniformity in single-cell WGS.

Featured Resources

Request a Quote

ResolveDNA® scDNAseqSingle-Cell DNA Sequencing Kits

Unlock the entire genome and enhance the discovery potential of your single-cell genomics with ResolveDNA. See what you have been missing

ResolveDNA Whole Genome Amplification Kits overcome the inherent challenges of low coverage uniformity in single-cell genomics that lead to increased sequencing costs and complex data analysis.

ResolveDNA Whole Genome Amplification Kits offer superior coverage and uniformity in single-cell WGS.

Featured Resources

Request a Quote

ResolveDNA® scDNAseq
Single-Cell DNA Sequencing Kits

Unlock the entire genome and enhance the discovery
potential of your single-cell genomics with ResolveDNA.
See what you have been missing