CAVACHON: a hierarchical variational autoencoder to integrate multi-modal single-cell data

Paired single-cell sequencing technologies enable the simultaneous measurement of complementary modalities of molecular data at single-cell resolution. Along with the advances in these technologies, many methods based on variational autoencoders have been developed to integrate these data. However, these methods do not explicitly incorporate prior biological relationships between the data modalities, which could significantly enhance modeling and interpretation. We propose a novel probabilistic learning framework that explicitly incorporates conditional independence relationships between multi-modal data as a directed acyclic graph using a generalized hierarchical variational autoencoder. We demonstrate the versatility of our framework across various applications pertinent to single-cell multi-omics data integration. These include the isolation of common and distinct information from different modalities, modality-specific differential analysis, and integrated cell clustering. We anticipate that the proposed framework can facilitate the construction of highly flexible graphical models that can capture the complexities of biological hypotheses and unravel the connections between different biological data types, such as different modalities of paired single-cell multi-omics data. The implementation of the proposed framework can be found in the repository https://github.com/kuijjerlab/CAVACHON.

Supervised Machine Learning with a Novel Pointwise Density Estimator

This article proposes a novel density estimation based algorithm for carrying out supervised machine learning. The proposed algorithm features O(n) time complexity for generating a classifier, where n is the number of sampling instances in the training dataset. This feature is highly desirable in contemporary applications that involve large and still growing databases. In comparison with the kernel density estimation based approaches, the mathe-matical fundamental behind the proposed algorithm is not based on the assump-tion that the number of training instances approaches infinite. As a result, a classifier generated with the proposed algorithm may deliver higher prediction accuracy than the kernel density estimation based classifier in some cases.

Supervised Machine Learning with a Novel Kernel Density Estimator

In recent years, kernel density estimation has been exploited by computer scientists to model machine learning problems. The kernel density estimation based approaches are of interest due to the low time complexity of either O(n) or O(n*log(n)) for constructing a classifier, where n is the number of sampling instances. Concerning design of kernel density estimators, one essential issue is how fast the pointwise mean square error (MSE) and/or the integrated mean square error (IMSE) diminish as the number of sampling instances increases. In this article, it is shown that with the proposed kernel function it is feasible to make the pointwise MSE of the density estimator converge at O(n^-2/3) regardless of the dimension of the vector space, provided that the probability density function at the point of interest meets certain conditions.