Visualization of genetic disease-phenotype similarities by multiple maps t-SNE with Laplacian regularization

From a phenotypic standpoint, certain types of diseases may prove to be difficult to accurately diagnose, due to specific combinations of confounding symptoms. Referred to as phenotypic overlap, these sets of disease-related symptoms suggest shared pathophysiological mechanisms. Few attempts have been made to visualize the phenotypic relationships between different human diseases from a machine learning perspective. The proposed research, it is anticipated, will visually assist researchers in quickly disambiguating symptoms which can confound the timely and accurate diagnosis of a disease.

Our method is primarily based on multiple maps t-SNE (mm-tSNE), which is a probabilistic method for visualizing data points in multiple low dimensional spaces. We improved mm-tSNE by adding a Laplacian regularization term and subsequently provide an algorithm for optimizing the new objective function. The advantage of Laplacian regularization is that it adopts clustering structures of variables and provides more sparsity to the estimated parameters.

In order to further assess our modified mm-tSNE algorithm from a comparative standpoint, we reexamined two social network datasets used by the previous authors. Subsequently, we apply our method on phenotype dataset. In all these cases, our proposed method demonstrated better performance than the original version of mm-tSNE, as measured by the neighbourhood preservation ratio.

Phenotype grouping reflects the nature of human disease genetics. Thus, phenotype visualization may be complementary to investigate candidate genes for diseases as well as functional relations between genes and proteins. These relationships can be modelled by the modified mm-tSNE method. The modified mm-tSNE can be applied directly in other domain including social and biological datasets.