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New Deep Learning Tool Accurately Classifies Tumor Types

Researchers from the NCI and Department of Energy (DOE) Collaboration have developed a deep learning tool for classifying human RNA-seq-based tumor types. This tool will be available for cancer researchers to use in the future, thanks to the Frederick National Laboratory for Cancer Research (FNLCR) Resource Curation Team and Argonne National Laboratory.

TULIP (Tumor cLassifIcation Predictor) is based on a one-dimensional, convolutional neural network framework derived from a previous NCI-DOE Collaboration resource, which aimed at accelerating advances in precision oncology and scientific computing.

Read the full article in Sage Journals.

Researchers updated the NCI-DOE resource, Tumor Classifier 1 (TC1), to include more tumor types (32 total) from NCI’s Genomic Data Commons. The team used CANcer Distributed Learning Environment (CANDLE), another NCI-DOE Collaboration resource, to optimize the underlying TC1 resource.

Confusion matrix of accuracy for 32 primary tumor types (X axis) and protein coding genes (Y axis). For the CNN-32 and CNN-32-PC models, the test accuracy was above 80% for 28 and 29 primary tumor types respectively and 90% for 25 primary tumor types. The primary tumor types with an accuracy of below 80% shared between both models include CHOL at 40% and READ at 0%.
Figure 1. Confusion matrix.

Overall, TULIP had at least a 95% accuracy on a test data set using protein-coding genes only. As shown in the confusion matrix in Figure 1, only two primary tumor types had below 50% accuracy. The reasons? Either the tumor types have highly similar RNA-seq profiles with other primary tumor types, or it’s due to a low sample size.

Dr. Satish Ranganathan Ganakammal, bioinformatics lead, explains that “the TULIP framework can be modified and adopted to perform machine learning (ML)-driven sample quality control in various RNA-seq analysis workflows.” The team recently adapted this framework to build an updated tumor tissue type classifier with canine-to-human common homologous genes. This was done to categorize canine RNA-seq samples based on the tumor tissue type. The work shows that developing cross-species ML models could have practical clinical applications, such as tumor subtype identification.

TULIP takes as input an RNA-seq count matrix, ideally from GDC, expressed as FPKM-UQ and outputs a file containing the predicted primary tumor types with their probability scores.
Figure 2. TULIP workflow.

Matthew Beyers, FNLCR’s manager of the Resource Curation Team, shared, “As more data becomes available, we plan to expand our classification framework to include those new tumor tissue subtypes (see Figure 2). As a part of our functionality enhancement efforts, we plan to add normal tissue data to classify normal and tumor tissue type samples and include other data types such as variant data.”

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