Introducing Enrichment v3.0 with Enhanced Variant Calling

Enrichment

Enrichment v3.0

The new Enrichment v3.0 BaseSpace® App (formerly called Isaac Enrichment) introduces major improvements and new features including:

  • Improved small variant calling
  • Copy number variant (CNV) calling
  • Structural variant calling
  • Somatic/low-frequency variant calling
  • Ability to start from FASTQ or BAM
  • GRCh38 reference added
  • Variant table CSV file including variant frequencies
  • Improved variant annotation engine
  • Improved metrics engine

The improved small variant calling using Starling is shown below for Coriell sample NA12878:

Input VCF SNV Recall SNV Precision SNV Non-assessed Indel Recall Indel Precision Indel Non-assessed
NA12878

(Enrichment v3.0)

90.83% 98.97% 5.35% 72.29% 93.19% 17.56%
NA12878

(Enrichment v2.1)

86.97% 99.54% 4.23% 68.09% 85.17% 21.14%
NA12878

(BWA Enrichment v2.1)

80.02% 99.80% 9.41% 58.80% 92.60% 18.71%

CNV calling is enabled in the Enrichment workflow using Canvas, an open-source tool. The screenshot below from IGV shows a 937,697 bp CNV loss found in a melanoma cancer sample around the chromosomal region chr9:125239269-126176965.  The sample data was obtained from NCBI’s Sequence Read Archive (accession ERR174231) using the SRA Import BaseSpace App.

This screenshot from IGV shows a CNV loss detected in sample ERR174231 at chr9:125239269-126176965

Project: SRA: ERP001844 (Exome Seq – CNV). Publication: Magi et al. Canvas v1.13.0

 

Somatic/low-frequency variant calling is enabled using the open-source Pisces tool.  The table below demonstrates the usefulness of this somatic calling tool:

Chr Pos Gene Known VF Pisces HD749 – VF Pisces HD749-Depth Pisces HD751-VF Pisces HD751-Depth
chr1 115256530 NRAS 12.00% 11.40% 166 10.60% 188
chr3 178936091 PIK3CA 10.00% 5.50% 109 5.40% 258
chr3 178952085 PIK3CA 15.50% 15.60% 141 24.40% 131
chr4 55599321 cKIT 9.00% 9.60% 366 13.60% 391
chr7 55241707 EGFR 24.50% 18.70% 359 24.20% 565
chr7 55242464 EGFR 1.50% NA NA NA NA
chr7 55249071 EGFR 1.00% NA NA NA NA
chr7 55259515 EGFR 3.00% NA NA 2.40% 763
chr7 140453136 BRAF 9.50% 9.20% 674 10.60% 800
chr12 25398281 KRAS 16.50% 14.10% 297 13.30% 400
chr12 25398284 KRAS 5.50% 5.30% 302 6.20% 402

Project: https://basespace.illumina.com/s/8m3R0Ndk84tt. Pisces v5.1.3.0, 1% VF cutoff

We’ve also updated our reporting to include read-, base-, and target-level enrichment metrics, as well as a new exportable variant table for simple visualization and to enable easier downstream filtering and processing.

enrichment-variants-table

The Enrichment v3.0 in-browser report produces an exportable variants table (CSV) listing all variants and annotation information.

We hope this update enables you to discover new insights. Stay tuned for more app announcements, and let us know if you have any questions.

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