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MD-ALL: an integrative platform for molecular diagnosis of B-acute lymphoblastic leukemia
- Source :
- Haematologica, Vol 109, Iss 6 (2023)
- Publication Year :
- 2023
- Publisher :
- Ferrata Storti Foundation, 2023.
-
Abstract
- B-acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEP) and various genetic lesions. With the application of transcriptome sequencing (RNA sequencing [RNA-seq]), multiple novel subtypes have been identified, which lead to an advanced B-ALL classification and risk-stratification system. However, the complexity of analyzing RNA-seq data for B-ALL classification hinders the implementation of the new B-ALL taxonomy. Here, we introduce Molecular Diagnosis of Acute Lymphoblastic Leukemia (MD-ALL), an integrative platform featuring sensitive and accurate B-ALL classification based on GEP and sentinel genetic alterations from RNA-seq data. In this study, we systematically analyzed 2,955 B-ALL RNA-seq samples and generated a reference dataset representing all the reported B-ALL subtypes. Using multiple machine learning algorithms, we identified the feature genes and then established highly sensitive and accurate models for B-ALL classification using either bulk or single-cell RNA-seq data. Importantly, this platform integrates multiple aspects of key genetic lesions acquired from RNA-seq data, which include sequence mutations, large-scale copy number variations, and gene rearrangements, to perform comprehensive and definitive B-ALL classification. Through validation in a hold-out cohort of 974 samples, our models demonstrated superior performance for B-ALL classification compared with alternative tools. Moreover, to ensure accessibility and user-friendly navigation even for users with limited or no programming background, we developed an interactive graphical user interface for this MD-ALL platform, using the R Shiny package. In summary, MD-ALL is a user-friendly B-ALL classification platform designed to enable integrative, accurate, and comprehensive B-ALL subtype classification. MD-ALL is available from https://github.com/gu-lab20/MD-ALL.
- Subjects :
- Diseases of the blood and blood-forming organs
RC633-647.5
Subjects
Details
- Language :
- English
- ISSN :
- 03906078 and 15928721
- Volume :
- 109
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- Haematologica
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.648588006f994528bf47b56f5ce05aba
- Document Type :
- article
- Full Text :
- https://doi.org/10.3324/haematol.2023.283706