Germline Nexome Panel
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Detect SNVs, INDELs and CNVs in a single, clinical-grade assay

Cell3 Target: Nexome

Capture more variants and increasing your diagnostic yield; without increasing your sequencing costs.

Unrivaled clinical relevance and enhanced content

Combat the challenges posed by whole exome sequencing by maximizing your diagnostic yield. Acquire coverage of important clinical targets from the major genetic databases including CNVs and non-coding regions associated with prenatal and postnatal disease.

Unifying variant analysis workflows with confidence

Validate and run one workflow for all variants including SNVs, INDELs and CNVs in a single, clinical-grade assay giving you the confidence to replace your array and Multiplex Ligation-dependent Probe Amplification (MLPA) based CNV analysis.

High precision CNV calling with minimal DNA input

Confidently call SNVs, INDELs and CNVs with high recall and precision from as little as 1 ng of DNA, unlocking prenatal or limited samples, without compromising on quality or robustness.

Exome sequencing for clinical genetics

Current clinical genetic workflows often involve undertaking multiple tests with different technologies such as chromosomal microarrays (CMA),  MLPA, fluorescent in situ hybridization (FISH) all often followed by NGS (exome sequencing). This increases associated test costs, cost per sample, time to results and has negative implications for the required amount of sample input.

Cell3 Target: Nexome has been developed combining our experience of exome panel design and input from experts in the field. As well as maximizing coverage of clinically relevant targets for SNVs and INDELs, Cell3 Target: Nexome is designed to cover exon level deletions and duplications providing an exome alternative to CMA and MLPA based CNV analysis.

In summary: it is a clinically enhanced human exome capture kit designed for robust whole-exome sequencing, and targeted copy number analysis, in one single test with the added benefit of a fast turnaround time, whilst removing the need for additional costly assays.

Comprehensive coverage of unrivaled clinically relevant regions, and enhanced content

Cell3 Target:Nexome is designed so excellent data coverage across the wider exome is easily attainable:

  • Protein coding regions of the human genome with additional clinically relevant non-coding regions
  • CCDS, ClinVar, GENCODE, RefSeq and ACMG73 databases (Figure 1) with enhanced probes to enable CNV detection at loci with known gene and exon level rearrangements
FIGURE1-1

Figure 1: Coverage of different databases by Cell3 Target: Nexome compared to other commercially available kits.

Increased diagnostic yield for exomes

Optimizing diagnostic yield from a genomics test is important so our Cell3 Target: Nexome panel has been designed to cover clinically relevant coding, and noncoding, regions to achieve outstanding coverage across the wider exome.

Boosted regions of the panel include:

  • Additional RefSeq transcripts across the Online Mendelian Inheritance in Man (OMIM) morbid set of genes1
  • Genes associated with pre and postnatal phenotypes (fetal anomalies)
  • Transcripts and extra exons associated with Early Infant Epileptic Encephalopathy (EIEE) genes for enhanced epilepsy diagnosis
  • Promoter, 5’ and 3’ UTR sequences for current OMIM morbid genes
  • Non-coding, disease-causing variants as reported by Smedley et al2,3
Figure-2-Coverage-of-targeted-gene-panels-and-variant-sets-2340x650-1-2048x569 (1)

Figure 2: Percentage coverage of gene transcripts and variants by Nexome compared to other commercially available kits.

Pharmacogenomic (PGx) marker inclusion

Cell3 Target: Nexome panel pharmacogenomic (PGx) marker inclusion and percent covered

Figure 3a: Nonacus

Company T pharmacogenomic (PGx) marker inclusion and percent covered

Figure 3b: Company T

Company I pharmacogenomic (PGx) marker inclusion and percent covered

Figure 3c: Company I

Precision and recall of SNVs and INDELs

Cell3 Target: Nexome detects significantly more truth variants present in the HG001 human genome reference standard than other exome captures, whilst maintaining superior precision and comparable recall for both SNVs and INDELs.

Precision and recall of SNVs detected by Nexome and other commercially available exome panels

Figure 4a: Precision and recall of SNVs detected by Cell3 Target: Nexome and other commercially available exome panels.

Total number of truth variants (SNVs) detected by Nexome and other commercially available exome panels

Figure 4b: Total number of truth variants (SNVs) detected by Cell3 Target: Nexome and other commercially available exome panels.

Precision and recall of Indels detected by Nexome and other commercially available exome panels

Figure 5a: Precision and recall of Indels detected by Cell3 Target: Nexome and other commercially available exome panels.

Total number of truth variants (Indels) detected by Nexome and other commercially available exome panels

Figure 5b: Total number of truth variants (Indels) detected by Cell3 Target: Nexome and other commercially available exome panels.

Precision CNV calling from exome sequencing using Cell3

Copy number variants account for ~10% of curated disease associated variants and are identified in ~10–20% of individuals with neurodevelopmental disorders.

  • Designed for superior CNV detection at loci known to have both gene and exon level rearrangements
  • Capable of detecting CNVs with sizes spanning from just a few exons up to multiple contiguous genes (~100 bp–40 Mb)
  • Evaluated using samples with known CNV events tested by either MLPA or CMA and confidently recalled CNV mutations from 50 bp (a single exon) up to 42 Mb
  • Detection of clinically relevant events is achieved with superior precision and recall and provides an exome alternative to CMA and MLPA based CNV analysis. (Table 1a and 1b)

Table 1a: Detection of MLPA-confirmed CNVs

Affected gene
CNV region
CNV size (bp)
CNV exons
CNV type
Bayes factor
FBN1 exons 29-65 74632 37 deletion 320.0
BRCA1 exons 1-23 77841 24 deletion 190.0
FBN1 exons 1-17 142063 18 deletion 300.0
BRCA1 exons 1-17 57876 18 deletion 200.0
BRCA1 exons 8-13 17956 6 deletion 40.4
BRCA1 exons 8-13 17956 6 deletion 82.4
BRCA2 exons 5-7 513 3 deletion 22.1
NSD1 exons 7-9 6034 3 deletion 34.5
FBN1 exons 60-62 3934 3 deletion 32.8
NSD1 exons 1-3 58095 3 deletion 54.8
BRCA2 exons 1-2 1054 2 deletion 28.3
BRCA1 exons 7-8 311 2 deletion 4.7
BRCA1 exons 8-9 1444 2 deletion 7.5
BRCA1 exon 16 211 1 deletion 14.5
BRCA1 exon 20 84 1 deletion 9.4

Table 1b: Detection of CMA-confirmed multi-gene CNVs.

CNV region
CNV size
CNV genes
CNV type
Bayes factor
13q14.2q32.1 42.0 367.0 deletion 2410.0
4p16.3p15.2 22.9 339.0 deletion 4620.0
20q11.22q13.12 11.3 244.0 deletion 7000.0
7p14.1p11.2 15.9 182.0 deletion 5040.0
1p36.32 3.7 140.0 deletion 2710.0
22q11.21 2.0 83.0 deletion 2890.0
8q23.1q24.12 11.8 71.0 deletion 1330.0
22q.11.21 2.2 64.0 duplication 1430.0
11p12p11.2 2.3 54.0 deletion 1240.0
7q11.23 1.4 38.0 deletion 2080.0
15q11.2 0.9 31.0 deletion 494.0
17p12 1.3 24.0 deletion 275.0
14q22.1 0.7 20.0 deletion 508.0
15q11.2 0.5 4.0 duplication 370.0
13q12.11 0.2 2.0 deletion 75.0

Delivers more content without increasing sequencing costs and additional assay testing

Detect more clinically relevant variants without increasing your sequencing costs.

  • Cell3 Target: Nexome panel targets just over 51 Mb of the human genome
  • Ensures that you can call up to 30% more variants than other commercially available exome panels and detect a wide range of CNVs
  • Probe design and superior performance (Table 2) means that, when compared to smaller commercially available exome panels, Nexome requires a similar, or less amount, of sequencing to achieve a mean coverage of 100× with 6.63 Gb

 

Combine workflows into one

  • Cell3 Target: Nexome panel presents an advanced alternative to MLPA by offering:
    • Increased coverage and improved targeting of classic MLPA regions
    • Surpasses Sanger sequencing
  • Cell3 Target: Nexome seamlessly delivers PMS2 sequencing, avoiding the need of additional analysis via PCR or MLPA

Table 2: Gb of sequence required to achieve mean coverage of 100x for Cell3 Target: Nexome and other commercially available exome products. Data was down sampled to 100x per sample for each exome panel.

Exome product
Panel size (Mb)
Percentage target covered at 1x
Gb required for mean 100x coverage
Percentage of bases on or near bait
Nexome 51.90 98.78% 6.63 94.18%
ExomeCG 51.60 98.78% 6.57 94.07%
CompanyT 36.70 97.42% 6.85 85.89%
Company I 45.20 98.15% 7.16 86.18%
CompanyI.D 34.10 98.49% 6.04 93.09%

Benefits from straight forward, automatable protocols

  • The Cell3 Target: Nexome kit contains all reagents for both library preparation and hybridization and capture.
  • The Cell3 Target workflow is simple and easy, requires as little as 1 ng of DNA and takes less than 10 hours, with less than two hours hands-on time.
  • It is designed with multiple stop points to provide flexibility within laboratory processing.
  • Library preparation can be run manually or automated (up to 96 samples in a single batch).
  • Indexes are available for up to 384 samples to facilitate high throughput laboratories, allow for flexible batch sizes and provide scalability across all Illumina sequencers.
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References

See our customer publications

Product support

Enrichment methodHybridisation and capture
Capture panel Size51.9 Mb
Sequencing platformIllumina
TargetsClinically relevant genes
Variant typesSNVs, indels and CNVs
Sample typegDNA from blood, saliva, amniotic fluid, tissue or FFPE, cfDNA
Input DNA requirements1-1000 ng
Expected percentage duplication~5-6%
Expected percentage on target (150 bp padding)~95%
Gb required for mean 100× coverage6.63
Multiplex capability384

Cell3 Target panels are available with one of two versions of our library preparation kits:

  • Fragmentation: for use with DNA (genomic, FF, FFPE)
  • Non-fragmentation: for use with cell-free DNA

ProductCatalog No.
Cell3™ Target: Nexome, Frag 16 samplesNGS_C3T_NEX_FR_16
Cell3™ Target: Nexome, Frag 96 samplesNGS_C3T_NEX_FR_96_A/B/C/D*
Cell3™ Target: Nexome, Non Frag 16 samplesNGS_C3T_NEX_NF_16
Cell3™ Target: Nexome, Non Frag 96 samplesNGS_C3T_NEX_NF_96_A/B/C/D*

* To provide flexibility in multiplexing samples, our 96-sample kits offer a choice in adapter plate:

A = Adapter plate with indexes 1-96
B = Adapter plate with indexes 97-192
C = Adapter plate with indexes 193-288
D = Adapter plate with indexes 289-384

What is meant by ‘clinically enhanced’ when referring to the Nexome panel?

Has the Cell3 Target:Nexome panel been designed with copy number variation in mind?

What depth of coverage should we aim for when planning our sequencing runs?

What sample types can be used with the Cell3 Target: Nexome panel?

Interested in our Cell3 Target: Nexome panel?