RanBALL: An Ensemble Machine Learning Framework for Accurate Subtype Identification of Pediatric B-Cell Acute...

As the most common pediatric malignancy, B-cell acute lymphoblastic leukemia (B-ALL) has multiple distinct subtypes characterized by recurrent and sporadic somatic and germline genetic alterations. Identifying B-ALL subtypes can facilitate risk stratification and enable tailored therapeutic design. Existing methods for B-ALL subtyping primarily depend on immunophenotyping, cytogenetic tests, and genomic profiling, which can be costly, complicated, and laborious. To overcome these challenges, RanBALL (an ensemble random projection-based model for identifying B-ALL subtypes) is presented, an accurate and cost-effective model for B-ALL subtype identification. By leveraging random projection (RP) and ensemble learning, RanBALL can preserve patient-to-patient distances after dimension reduction and yield robustly accurate classification performance for B-ALL subtyping. Benchmarking results based on >1700 B-ALL patients demonstrate that RanBALL achieves remarkable performance (accuracy: 0.93, F1-score: 0.93, and Matthews correlation coefficient: 0.93), significantly outperforming state-of-the-art methods like ALLSorts in terms of all performance metrics. In addition, RanBALL performs better than t-SNE in terms of visualizing B-ALL subtype information. We believe RanBALL will facilitate the discovery of B-ALL subtype-specific marker genes and therapeutic targets to have consequential positive impacts on downstream risk stratification and tailored treatment design is believed. To extend its applicability and impacts, a Python-based RanBALL package is available at https://github.com/wan-mlab/RanBALL.