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Bioinformatics. 2015 Dec 1;31(23):3844-6. doi: 10.1093/bioinformatics/btv456. Epub 2015 Aug 6.

ARResT/AssignSubsets: a novel application for robust subclassification of chronic lymphocytic leukemia based on B cell receptor IG stereotypy.

Author information

1
CEITEC-Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
2
Division of Molecular Oncology and Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy.
3
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden and.
4
Institute of Applied Biosciences, Center for Research and Technology Hellas, Thessaloniki, Greece Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden and.

Abstract

MOTIVATION:

An ever-increasing body of evidence supports the importance of B cell receptor immunoglobulin (BcR IG) sequence restriction, alias stereotypy, in chronic lymphocytic leukemia (CLL). This phenomenon accounts for ∼30% of studied cases, one in eight of which belong to major subsets, and extends beyond restricted sequence patterns to shared biologic and clinical characteristics and, generally, outcome. Thus, the robust assignment of new cases to major CLL subsets is a critical, and yet unmet, requirement.

RESULTS:

We introduce a novel application, ARResT/AssignSubsets, which enables the robust assignment of BcR IG sequences from CLL patients to major stereotyped subsets. ARResT/AssignSubsets uniquely combines expert immunogenetic sequence annotation from IMGT/V-QUEST with curation to safeguard quality, statistical modeling of sequence features from more than 7500 CLL patients, and results from multiple perspectives to allow for both objective and subjective assessment. We validated our approach on the learning set, and evaluated its real-world applicability on a new representative dataset comprising 459 sequences from a single institution.

AVAILABILITY AND IMPLEMENTATION:

ARResT/AssignSubsets is freely available on the web at http://bat.infspire.org/arrest/assignsubsets/

CONTACT:

nikos.darzentas@gmail.com.

SUPPLEMENTARY INFORMATION:

Supplementary data are available at Bioinformatics online.

PMID:
26249808
DOI:
10.1093/bioinformatics/btv456
[Indexed for MEDLINE]

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