MAPE-PPI: Towards Effective and Efficient Protein-Protein Interaction Prediction via Microenvironment-Aware Protein Embedding

Protein-Protein Interactions (PPIs) are fundamental in various biological processes and play a key role in life activities. The growing demand and cost of experimental PPI assays require computational methods for efficient PPI prediction. While existing methods rely heavily on protein sequence for PPI prediction, it is the protein structure that is the key to determine the interactions. To take both protein modalities into account, we define the microenvironment of an amino acid residue by its sequence and structural contexts, which describe the surrounding chemical properties and geometric features. In addition, microenvironments defined in previous work are largely based on experimentally assayed physicochemical properties, for which the "vocabulary" is usually extremely small. This makes it difficult to cover the diversity and complexity of microenvironments. In this paper, we propose Microenvironment-Aware Protein Embedding for PPI prediction (MPAE-PPI), which encodes microenvironments into chemically meaningful discrete codes via a sufficiently large microenvironment "vocabulary" (i.e., codebook). Moreover, we propose a novel pre-training strategy, namely Masked Codebook Modeling (MCM), to capture the dependencies between different microenvironments by randomly masking the codebook and reconstructing the input. With the learned microenvironment codebook, we can reuse it as an off-the-shelf tool to efficiently and effectively encode proteins of different sizes and functions for large-scale PPI prediction. Extensive experiments show that MAPE-PPI can scale to PPI prediction with millions of PPIs with superior trade-offs between effectiveness and computational efficiency than the state-of-the-art competitors.

HONEM: Network Embedding Using Higher-Order Patterns in Sequential Data

Representation learning offers a powerful alternative to the oft painstaking process of manual feature engineering, and as a result, has enjoyed considerable success in recent years. This success is especially striking in the context of graph mining, since networks can take advantage of vast troves of sequential data to encode information about interactions between entities of interest. But how do we learn embeddings on networks that have higher-order and sequential dependencies? Existing network embedding methods naively assume the Markovian property (first-order dependency) for node interactions, which may not capture the time-dependent and longer-range underlying complex interactions of the raw data. To address the limitation of current methods, we propose a network embedding method for higher-order networks (HON). We demonstrate that the higher-order network embedding (HONEM) method is able to extract higher-order dependencies from HON to construct the higher-order neighborhood matrix of the network, while existing methods are not able to capture these higher-order dependencies. We show that our method outperforms other state-of-the-art methods in node classification, network reconstruction, link prediction, and visualization.