Qlucore

ALL Classifier Model

Subtype classification of Acute Lymphoblastic Leukemia RNA-seq samples

ALL Model

Acute Lymphoblastic Leukemia

ALL model

 

Acute lymphoblastic leukemia (ALL)  is the most common acute leukemia in children and accounts for approximately 30% of all cases of acute leukemia in adults. This disease is characterized by several genetic alterations of great clinical diagnostic importance, as recognized by the current WHO classification.

Routine Diagnostics of ALL


Today more than four different methods (e.g. chromosome banding analysis, genetic assays identifying SNVs and CNVs, FISH) are used in routine diagnostics for diagnosis of ALL. These requires several different competences, instruments and are collectively time consuming.​

 

A number of gene fusions in ALL can be targeted with specific drugs with improved outcomes for patients, or used for risk stratification, making it critical to detect such alterations at the diagnostic workup. In this context, RNA-sequencing is becoming an increasingly important diagnostic tool as it can detect gene fusions in an unbiased manner and aid the subtype classification based on distinct gene expression signatures.

Chromsomal banding analysis

FISH analysis

RNA-seq - emerging clinical diagnostic tool​ for ALL

mRNA

RNA sequencing allows measuring of two key parameters for diagnostics of Acute Lymphoblastic Leukemia which can be used for subtype classification:

1) chimeric gene fusions 
2) gene expression levels

Given high resolution enables the detection of most clinically relevant genetic alterations, the decreasing sequencing costs associated with such tests, and amenability to automatization we will see a wide adoption of RNA-sequencing in the clinical setting with several frontline laboratories already offering such analyses.

Read more about the power of integrating transcriptomics in diagnostics and precision medicine:
 "Transcriptomics paving the way for improved diagnostics and precision medicine of acute leukemia" Fioretos et al.

Short interview with Key Opinion Leader Thoas Fioretos - Professor in Clinical Genetics

The great majority of ALLs are characterized by gene fusions or display a distinct gene expression signature that can be used for classification purposes. Watch short interview about the benefits of using RNA seq for diagnosis of ALL. 

Qlucore's subtype classfier model for ALL

Scalable and visualization-based diagnostics solution from data to report, based on RNA-seq and standard NGS workflows.

The model includes:
ALL model

 

  • AI powered subtype classification of individual samples, complemented by flexible visualizations.

  • User-friendly interface for exploration of detected gene fusions, with no need for bioinformatics expertise.  

  • Integration with gene fusion databases (Mitelman and Tumorfusions) for comprehensive analysis and evaluation 

  • Easy filtering options on relevant quality metrics, location and more, to quickly identify the fusions of most relevance.

  • Automatic generation of highly customizable reports.  

Performance

The gene expression classifier model for pediatric Acute Lymphoblastic Leukemia allows gene expression based subtype classification of the B-cell leukemias listed below, and with the gene fusions analysis support further stratification is possible. 

1. High hyperdiploidy*
2. ETV6/RUNX1* + ETV6/RUNX1-like
3. KMT2A(MLL)-rearranged (MLL)*
4. TCF3/PBX1*
5. BCR/ABL1* + BCR/ABL1-like*
6. DUX4-rearranged

*RECOGNIZED BY THE CURRENT WHO CLASSIFICATION

 

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The performance plot illustrates the accuracy of the gene expression classification from validation with external data. Note: These results are preliminary and may change.

 

White paper - Genetic classification of ALL

RNA-sequencing as an emerging clinical diagnostic tool.

Supported data

supported data
  • RNA-seq data, reference genome hg 19. 

  • Supported fusion callers 

    • Fusion-Catcher 

    • STAR-Fusion 

    • Arriba

 

Work is ongoing to support more data formats. 

Short introduction video

Watch here

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