Heterogeneous latent transfer learning in Gaussian graphical models

Gaussian graphical models (GGMs) are useful for understanding the complex relationships between biological entities. Transfer learning can improve the estimation of GGMs in a target dataset by incorporating relevant information from related source studies. However, biomedical research often involves intrinsic and latent heterogeneity within a study, such as heterogeneous subpopulations. This heterogeneity can make it difficult to identify informative source studies or lead to negative transfer if the source study is improperly used. To address this challenge, we developed a heterogeneous latent transfer learning (Latent-TL) approach that accounts for both within-sample and between-sample heterogeneity. The idea behind this approach is to "learn from the alike" by leveraging the similarities between source and target GGMs within each subpopulation. The Latent-TL algorithm simultaneously identifies common subpopulation structures among samples and facilitates the learning of target GGMs using source samples from the same subpopulation. Through extensive simulations and real data application, we have shown that the proposed method outperforms single-site learning and standard transfer learning that ignores the latent structures. We have also demonstrated the applicability of the proposed algorithm in characterizing gene co-expression networks in breast cancer patients, where the inferred genetic networks identified many biologically meaningful gene-gene interactions.