Drug combinations are required to treat advanced cancers and other complex diseases. Compared with monotherapy, combination treatments can enhance efficacy and reduce toxicity by lowering the doses of single drugs-and there especially synergistic combinations are of interest. Since drug combination screening experiments are costly and time-consuming, reliable machine learning models are needed for prioritizing potential combinations for further studies. Most of the current machine learning models are based on scalar-valued approaches, which predict individual response values or synergy scores for drug combinations. We take a functional output prediction approach, in which full, continuous dose-response combination surfaces are predicted for each drug combination on the cell lines. We investigate the predictive power of the recently proposed comboKR method, which is based on a powerful input-output kernel regression technique and functional modeling of the response surface. In this work, we develop a scaled-up formulation of the comboKR, which also implements improved modeling choices: we (1) incorporate new modeling choices for the output drug combination response surfaces to the comboKR framework, and (2) propose a projected gradient descent method to solve the challenging pre-image problem that is traditionally solved with simple candidate set approaches. We provide thorough experimental analysis of comboKR 2.0 with three real-word datasets within various challenging experimental settings, including cases where drugs or cell lines have not been encountered in the training data. Our comparison with synergy score prediction methods further highlights the relevance of dose-response prediction approaches, instead of relying on simple scoring methods.

Abstract In this paper we propose a novel variable selection method for two-view settings, or for vector-valued supervised learning problems. Our framework is able to handle extremely large scale selection tasks, where number of data samples could be even millions. In a nutshell, our method performs variable selection by iteratively selecting variables that are highly correlated with the output variables, but which are not correlated with the previously chosen variables. To measure the correlation, our method uses the concept of projection operators and their algebra. With the projection operators the relationship, correlation, between sets of input and output variables can also be expressed by kernel functions, thus nonlinear correlation models can be exploited as well. We experimentally validate our approach, showing on both synthetic and real data its scalability and the relevance of the selected features.

scikit-multimodallearn is a Python library for multimodal supervised learning, licensed under Free BSD, and compatible with the well-known scikit-learn toolbox (Fabian Pedregosa, 2011). This paper details the content of the library, including a specific multimodal data formatting and classification and regression algorithms. Use cases and examples are also provided.

We consider the kernel completion problem with the presence of multiple views in the data. In this context the data samples can be fully missing in some views, creating missing columns and rows to the kernel matrices that are calculated individually for each view. We propose to solve the problem of completing the kernel matrices with Cross-View Kernel Transfer (CVKT) procedure, in which the features of the other views are transformed to represent the view under consideration. The transformations are learned with kernel alignment to the known part of the kernel matrix, allowing for finding generalizable structures in the kernel matrix under completion. Its missing values can then be predicted with the data available in other views. We illustrate the benefits of our approach with simulated data, multivariate digits dataset and multi-view dataset on gesture classification, as well as with real biological datasets from studies of pattern formation in early Drosophila melanogaster embryogenesis.

We consider the problem of operator-valued kernel learning and investigate the possibility of going beyond the well-known separable kernels. Borrowing tools and concepts from the field of quantum computing, such as partial trace and entanglement, we propose a new view on operator-valued kernels and define a general family of kernels that encompasses previously known operator-valued kernels, including separable and transformable kernels. Within this framework, we introduce another novel class of operator-valued kernels called entangled kernels that are not separable. We propose an efficient two-step algorithm for this framework, where the entangled kernel is learned based on a novel extension of kernel alignment to operator-valued kernels. We illustrate our algorithm with an application to supervised dimensionality reduction, and demonstrate its effectiveness with both artificial and real data for multi-output regression.

The trace regression model, a direct extension of the well-studied linear regression model, allows one to map matrices to real-valued outputs. We here introduce an even more general model, namely the partial-trace regression model, a family of linear mappings from matrix-valued inputs to matrix-valued outputs; this model subsumes the trace regression model and thus the linear regression model. Borrowing tools from quantum information theory, where partial trace operators have been extensively studied, we propose a framework for learning partial trace regression models from data by taking advantage of the so-called low-rank Kraus representation of completely positive maps. We show the relevance of our framework with synthetic and real-world experiments conducted for both i) matrix-to-matrix regression and ii) positive semidefinite matrix completion, two tasks which can be formulated as partial trace regression problems.

We consider the problem of operator-valued kernel learning and investigate the possibility of going beyond the well-known separable kernels. Borrowing tools and concepts from the field of quantum computing, such as partial trace and entanglement, we propose a new view on operator-valued kernels and define a general family of kernels that encompasses previously known operator-valued kernels, including separable and transformable kernels. Within this framework, we introduce another novel class of operator-valued kernels called entangled kernels that are not separable. We propose an efficient two-step algorithm for this framework, where the entangled kernel is learned based on a novel extension of kernel alignment to operator-valued kernels. The utility of the algorithm is illustrated on both artificial and real data.

We consider the problem of metric learning for multi-view data and present a novel method for learning within-view as well as between-view metrics in vector-valued kernel spaces, as a way to capture multi-modal structure of the data. We formulate two convex optimization problems to jointly learn the metric and the classifier or regressor in kernel feature spaces. An iterative three-step multi-view metric learning algorithm is derived from the optimization problems. In order to scale the computation to large training sets, a block-wise Nyström approximation of the multi-view kernel matrix is introduced. We justify our approach theoretically and experimentally, and show its performance on real-world datasets against relevant state-of-the-art methods.