gneSeqCOO: A novel method for classifying diffuse large B-cell lymphoma cell of origin based on bulk tumor RNA sequencing profiles Journal Article
| Authors: | Harris, W.; Cao, Y.; Morschhauser, F.; Salles, G.; Jiang, Y.; Bottos, A.; Lenz, G.; Bolen, C. R. |
| Article Title: | gneSeqCOO: A novel method for classifying diffuse large B-cell lymphoma cell of origin based on bulk tumor RNA sequencing profiles |
| Abstract: | The cell of origin (COO) classification is an expression-based tumor algorithm identifying molecular subtypes of diffuse large B-cell lymphoma (DLBCL) with distinct prognostic characteristics. Traditional immunohistochemical methods for classifying COO subtypes have poor concordance and limited prognostic value in frontline DLBCL. In contrast, RNA-based metrics like the NanoString Lymphoma Subtyping Test (LST) define more robust subtypes with validated prognostic associations. This study introduces gneSeqCOO, an algorithm using bulk RNA Sequencing (RNASeq) profiles of individual tumor biopsies for COO classification based on a fixed reference. This method produced consistent per-sample results and was robust to variation in RNA quality and sequencing bias. Validation in >1000 DLBCL samples showed high concordance with the NanoString LST assay, even in cohorts containing only one COO subtype. gneSeqCOO presents a robust and versatile alternative to existing assays, potentially reducing the need for additional samples where RNASeq was already generated. The package is available at https://github.com/Genentech/gneSeqCOO. © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | immunohistochemistry; controlled study; human tissue; major clinical study; genetics; gold standard; gene; gene expression; classification; gene expression profiling; computational biology; tumor biopsy; immunofluorescence; pathology; algorithms; tumor marker; rna; germinal center; algorithm; diagnosis; benchmarking; lymphoma, large b-cell, diffuse; sequence analysis, rna; bioinformatics; software; transcriptome; complementary dna; diffuse large b-cell lymphoma; rna sequence; clinical trial (topic); housekeeping gene; principal component analysis; gene expression level; procedures; diffuse large b cell lymphoma; dna library; predictive model; humans; prognosis; human; article; rna sequencing; biomarkers, tumor; cell of origin classification; b cell lymphoma cell |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 66 |
| Issue: | 5 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2025-01-01 |
| Start Page: | 898 |
| End Page: | 905 |
| Language: | English |
| DOI: | 10.1080/10428194.2024.2446613 |
| PUBMED: | 39792708 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
