Increased Sensitivity of Diagnostic Mutation Detection by Re-Analysis Incorporating Local

Increased sensitivity of diagnostic mutation detection by re-analysis incorporating local reassembly of sequence reads

Molecular Diagnosis & Therapy

Christopher M. Watson*, Nick Camm, Laura A. Crinnion, Samuel Clokie, Rachel L. Robinson, Julian Adlard, Ruth Charlton, Alexander F. Markham, Ian M. Carr, David T. Bonthron

*Yorkshire Regional Genetics Service and MRC Single Cell Functional Genomics Centre/MRC Medical Bioinformatics Centre, Leeds Institute for Data Analytics, University of Leeds St. James’s University Hospital, Leeds, LS9 7TF, United Kingdom. Email: .

Supplementary Table 1: The detection sensitivity for 7 insertion/deletion variants using three different variant callers on pre- and post-ABRA aligned BAM files.

Sample ID / Gene
(c.Nomen) / Sequence
affected / 101-bp read length / 151-bp read length
UniGeno / HaploCall / Platypus / UniGeno / HaploCall / Platypus
- / + / - / + / - / + / - / + / - / + / - / +
1 / BRCA2
(c.8736_8744del) / 9 bp deleted / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔
2 / MLH1
(c.197_207+20del) / 31 bp deleted / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔
3 / BRCA1
(c.1175_1214del) / 40 bp deleted / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔
4 / PMS2
(c.24-12_107delinsAAAT) / 96 bp deleted, 4 bp inserted / ✗ / ✔ / ✗* / ✔ / ✗ / ✔ / ✗ / ✔ / ✗* / ✔ / ✗ / ✔
5 / PTEN
(c.342_364dup) / 23 bp duplicated / ✗ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔
6 / CDKN2A
(c.9_32dup) / 24 bp duplicated / ✗ / ✔ / ✔ / ✔ / ✗ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔ / ✔
7 / SLC26A4
(c.1416_1417ins37) / 37 bp duplicated / N.D. / N.D. / N.D. / N.D. / N.D. / N.D. / ✗ / ✔ / ✔ / ✔ / ✔ / ✔

Alignment BAM files were assessed before (-) and after (+) ABRA processing. *:Variant detected following inclusion of the argument

‘--dontTrimActiveRegions’.N.D.: No data available.