SWIGH-SCORE: A translational light-weight approach in computational detection of rearranged immunoglobulin heavy chain to be used in monoclonal lymphoproliferative disorders
Marcus Høy Hansen,
Markus Maagaard,
Oriane Cédile,
Charlotte Guldborg Nyvold
Affiliations
Marcus Høy Hansen
Haematology-Pathology Research Laboratory, Research Unit of Haematology, Department of Hematology, and Research Unit of Pathology, Department of Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark; Corresponding author: Marcus Høy Hansen, Ph.D., J.B. Winsløws Vej 15, 3rd fl., 5000 Odense C, Denmark.
Markus Maagaard
Haematology-Pathology Research Laboratory, Research Unit of Haematology, Department of Hematology, and Research Unit of Pathology, Department of Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark
Oriane Cédile
Haematology-Pathology Research Laboratory, Research Unit of Haematology, Department of Hematology, and Research Unit of Pathology, Department of Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark; OPEN, Odense Patient data Explorative Network, Haematology-Pathology Research Laboratory, Odense University Hospital, Odense, Denmark
Charlotte Guldborg Nyvold
Haematology-Pathology Research Laboratory, Research Unit of Haematology, Department of Hematology, and Research Unit of Pathology, Department of Pathology, University of Southern Denmark and Odense University Hospital, Odense, Denmark; OPEN, Odense Patient data Explorative Network, Haematology-Pathology Research Laboratory, Odense University Hospital, Odense, Denmark
We present a lightweight tool for clonotyping and measurable residual disease (MRD) assessment in monoclonal lymphoproliferative disorders. It is a translational method that enables computational detection of rearranged immunoglobulin heavy chain gene sequences. • The swigh-score clonotyping tool emphasizes parallelization and applicability across sequencing platforms. • The algorithm is based on an adaptation of the Smith-Waterman algorithm for local alignment of reads generated by 2nd and 3rd generation of sequencers.For method validation, we demonstrate the targeted sequences of immunoglobulin heavy chain genes from diagnostic bone marrow using serial dilutions of CD138+ plasma cells from a patient with multiple myeloma. Sequencing libraries from diagnostic samples were prepared for the three sequencing platforms, Ion S5 (Thermo Fisher Scientific), MiSeq (Illumina), and MinION (Oxford Nanopore), using the LymphoTrack assay. Basic quality filtering was performed, and a Smith-Waterman-based swigh-score algorithm was developed in shell and C for clonotyping and MRD assessment using FASTQ data files. Performance is demonstrated across the three different sequencing platforms.
