Sparse representation learning derives biological features with explicit gene weights from the Allen Mouse Brain...

Unsupervised learning methods are commonly used to detect features within transcriptomic data and ultimately derive meaningful representations of biology. Contributions of individual genes to any feature however becomes convolved with each learning step, requiring follow up analysis and validation to understand what biology might be represented by a cluster on a low dimensional plot. We sought learning methods that could preserve the gene information of detected features, using the spatial transcriptomic data and anatomical labels of the Allen Mouse Brain Atlas as a test dataset with verifiable ground truth. We established metrics for accurate representation of molecular anatomy to find sparse learning approaches were uniquely capable of generating anatomical representations and gene weights in a single learning step. Fit to labeled anatomy was highly correlated with intrinsic properties of the data, offering a means to optimize parameters without established ground truth. Once representations were derived, complementary gene lists could be further compressed to generate a low complexity dataset, or to probe for individual features with >95% accuracy. We demonstrate the utility of sparse learning as a means to derive biologically meaningful representations from transcriptomic data and reduce the complexity of large datasets while preserving intelligible gene information throughout the analysis.