mmSYGNAL-risk-prediction-models

ML risk prediction models generated from mmSYGNAL

mmSYGNAL risk prediction

Tutorial for applying mmSYGNAL risk models to a new patient diagnosed with multiple myeloma. Risk models were generated separately based on the genetic abnormality subtypes patients in our training cohort exhibited. The agnostic model was generated with all patients in training cohort regardless of subtype and is appropriate for patients that do not exhibit a relevant genetic subtype or when subtype information is not obtainable.

mmSYGNAL risk models

See analysis/risk_model_tutorial.nb.html for code.

The following risk models are available.

no subtype

1. agnostic

cytogentic subtypes

2. amp(1q)
3. del(13)
4. del(1p)
5. t(4;14)

RNAseq subtypes

5. FGFR3

Steps required for pipeline

1. Generate gene expression data for patient and annotate with ensembl gene ids. RNAseq data is recommended but mmSYGNAL also functions with microarray data.

2. Apply mmSYGNAL model to gene expression data to generate program activity. See 'Wall et al, Genetic program activity delineates risk, relapse, and therapy responsiveness in multiple myeloma, Precision Oncology, 2021' for instructions on how to apply mmSYGNAL.

3. Format patient's program activity into a data.frame where the row is the patient's program activity column titles are the program label (0 to 140).

4. Identify which genetic abnormality risk subtypes the patient exhibits and apply the appropriate risk models. See code below for examples.

5. If desired choose only the highest grade models (A > B > C) if a patient exhbits multiple subtypes. If a patient shows multiple subtypes of the same grade then take the mean of the risk scores.

6. The patients risk classification is generated based on their predicted risk score as shown below:

• low risk: < 0.5

• high risk: >= 0.5 and < 0.6

• extreme risk: >= 0.6