Comprehensive review and evaluation of computational methods for identifying FLT3-internal tandem duplication in acute myeloid leukaemia

Danyang Yuan; Xiaoyu He; Xinyin Han; Chunyan Yang; Fei Liu; Shuying Zhang; Haijing Luan; Ruilin Li; Jiayin He; Xiaohong Duan; Dongliang Wang; Qiming Zhou; Sujun Gao; Beifang Niu

doi:10.1093/bib/bbab099

Comprehensive review and evaluation of computational methods for identifying FLT3-internal tandem duplication in acute myeloid leukaemia

Brief Bioinform. 2021 Sep 2;22(5):bbab099. doi: 10.1093/bib/bbab099.

Authors

Danyang Yuan¹, Xiaoyu He², Xinyin Han³, Chunyan Yang⁴, Fei Liu⁵, Shuying Zhang⁶, Haijing Luan⁷, Ruilin Li⁸, Jiayin He⁹, Xiaohong Duan¹⁰, Dongliang Wang¹¹, Qiming Zhou¹², Sujun Gao¹³, Beifang Niu¹⁴

Affiliations

¹ Computer Network Information Center, Chinese Academy of Sciences. She is mainly engaged in leukaemia-related bioinformatics and cancer genomics research. Her affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China.
² Computer Network Information Center, Chinese Academy of Sciences. She is mainly engaged in research related to the cancer genome and construction of the Chinese Cancer Genome Database. Her affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China.
³ Computer Network Information Center, Chinese Academy of Sciences. He is mainly engaged in cancer genomics research focusing on the precise detection of tumour immunotherapy biomarkers. His affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China.
⁴ Vice Director of the Laboratory of ChosenMed Technology (Beijing) Co., Ltd. She is mainly engaged in research regarding solid tumours and haematologic malignancy using multiple approaches, including next-generation sequencing. Her affiliation is with ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.
⁵ bioinformatics analysis engineer of ChosenMed Technology (Beijing) Co., Ltd. She is mainly engaged in the collection of biological information and analysis of genomic and cancer data or other biological information. Her affiliation is with ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.
⁶ Computer Network Information Center, Chinese Academy of Sciences. Her research mainly focuses on the cancer genome and bioinformatics. Her affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China.
⁷ Computer Network Information Center, Chinese Academy of Sciences. She is mainly engaged in researching cancers of unknown primary sites (CUP) based on deep learning. Her affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China.
⁸ Computer Network Information Center, Chinese Academy of Sciences. Her research interests include high-performance computing and bioinformatics. Her affiliation is with Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China.
⁹ George Washington University. She is currently researching at the Computer Network Information Center, Chinese Academy of Sciences. Her research interests include biostatistics and computational statistics. Her affiliation is with Computer Network Information Center, Chinese Academy of Sciences, Beijing 100190, China.
¹⁰ Laboratory of ChosenMed Technology (Beijing) Co., Ltd. She is mainly engaged in the research of solid tumours and haematologic malignancies using multiple approaches, including next-generation sequencing. Her affiliation is with ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.
¹¹ Harbin Medical University. He is now the Chief Medical Officer of ChosenMed Technology (Beijing). His research mainly focuses on the mining and verification of molecular markers for tumour therapy. His affiliation is with ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.
¹² CTO of ChosenMed Technology (Beijing) Co., Ltd. He is mainly engaged in the development of new molecular diagnostics technologies in genetic testing. His affiliation is with ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.
¹³ Department of Haematology, The First Hospital of Jilin University. Her research mainly focuses on the experimental and clinical research of malignant haematological disorders and haematopoietic stem cell transplantation. Her affiliation is with Department of Haematology, The First Hospital of Jilin University, Changchun 130021, China.
¹⁴ Computer Network Information Center, Chinese Academy of Sciences. His research interests include cancer genomics, metagenomics, and the development of computational tools for working with data from next-generation sequencing technologies. His affiliation is with Computer Network Information Center, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Beijing 100190, China, ChosenMed Technology (Beijing) Co., Ltd., Beijing 100176, China.

PMID: 33851200
DOI: 10.1093/bib/bbab099

Abstract

Internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3-ITD) constitutes an independent indicator of poor prognosis in acute myeloid leukaemia (AML). AML with FLT3-ITD usually presents with poor treatment outcomes, high recurrence rate and short overall survival. Currently, polymerase chain reaction and capillary electrophoresis are widely adopted for the clinical detection of FLT3-ITD, whereas the length and mutation frequency of ITD are evaluated using fragment analysis. With the development of sequencing technology and the high incidence of FLT3-ITD mutations, a multitude of bioinformatics tools and pipelines have been developed to detect FLT3-ITD using next-generation sequencing data. However, systematic comparison and evaluation of the methods or software have not been performed. In this study, we provided a comprehensive review of the principles, functionality and limitations of the existing methods for detecting FLT3-ITD. We further compared the qualitative and quantitative detection capabilities of six representative tools using simulated and biological data. Our results will provide practical guidance for researchers and clinicians to select the appropriate FLT3-ITD detection tools and highlight the direction of future developments in this field. Availability: A Docker image with several programs pre-installed is available at https://github.com/niu-lab/docker-flt3-itd to facilitate the application of FLT3-ITD detection tools.

Keywords: FLT3-ITD; acute myeloid leukaemia; bioinformatics; next-generation sequencing.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Acute Disease
Biomarkers, Tumor / genetics*
Computational Biology / methods*
Gene Duplication*
High-Throughput Nucleotide Sequencing / methods
Humans
Leukemia, Myeloid / diagnosis
Leukemia, Myeloid / genetics*
Mutation
Tandem Repeat Sequences / genetics*
fms-Like Tyrosine Kinase 3 / genetics*

Substances

Biomarkers, Tumor
FLT3 protein, human
fms-Like Tyrosine Kinase 3