Multi-omic data provides multiple views of the same patients. Integrative analysis of multi-omic data is crucial to elucidate the molecular underpinning of disease etiology. However, multi-omic data has the “big p, small N” problem (the number of features is large, but the number of samples is small), it is challenging to train a complicated machine learning model from the multi-omic data alone and make it generalize well. Here we propose a framework termed Multi-view Factorization AutoEncoder with network constraints to integrate multi-omic data with domain knowledge (biological interaction networks). Our framework employs deep representation learning to learn feature embeddings and patient embeddings simultaneously, enabling us to integrate feature interaction network and patient view similarity network constraints into the training objective. The whole framework is end-to-end differentiable. We applied our approach to two TCGA datasets and achieved satisfactory results on predicting disease Progression-Free Interval (PFI) event.
Our work is closely related to multi-modality deep learning @cite_9 , which had been successfully applied to combine audio and video features @cite_0 by employing shared feature representations. In addition to integrating multi-modality data, our proposed approach can learn feature representations and object (patient) embeddings simultaneously, which enables us to integrate feature interaction networks as domain knowledge, as well as to enforce view similarity network constraints in the training objective. Besides adding regularizers into training objectives, another way to incorporate biological networks into the model is to directly encode biological networks into the model architecture @cite_2 @cite_10 . However, these approaches usually require using subcellular hierarchical molecular networks, which we do not have high-quality data available for humans (though a few datasets are available for simple organisms such as bacteria). Given the fact that most human biological interaction networks such as protein-protein interaction networks are highly incomplete and noisy, adding network regularizers to the training objective instead of directly encoding the noisy interaction network into the model architecture provides more flexibility and alleviates the risk of adopting potentially wrong model architecture.
@cite_0 @cite_9 @cite_10 @cite_2
2184188583 2619383789 2790179710 2810565934
Deep networks have been successfully applied to unsupervised feature learning for single modalities (e.g., text, images or audio). In this work, we propose a novel application of deep networks to learn features over multiple modalities. We present a series of tasks for multimodal learning and show how to train deep networks that learn features to address these tasks. In particular, we demonstrate cross modality feature learning, where better features for one modality (e.g., video) can be learned if multiple modalities (e.g., audio and video) are present at feature learning time. Furthermore, we show how to learn a shared representation between modalities and evaluate it on a unique task, where the classifier is trained with audio-only data but tested with video-only data and vice-versa. Our models are validated on the CUAVE and AVLetters datasets on audio-visual speech classification, demonstrating best published visual speech classification on AVLetters and effective shared representation learning. Our experience of the world is multimodal - we see objects, hear sounds, feel texture, smell odors, and taste flavors. Modality refers to the way in which something happens or is experienced and a research problem is characterized as multimodal when it includes multiple such modalities. In order for Artificial Intelligence to make progress in understanding the world around us, it needs to be able to interpret such multimodal signals together. Multimodal machine learning aims to build models that can process and relate information from multiple modalities. It is a vibrant multi-disciplinary field of increasing importance and with extraordinary potential. Instead of focusing on specific multimodal applications, this paper surveys the recent advances in multimodal machine learning itself and presents them in a common taxonomy. We go beyond the typical early and late fusion categorization and identify broader challenges that are faced by multimodal machine learning, namely: representation, translation, alignment, fusion, and co-learning. This new taxonomy will enable researchers to better understand the state of the field and identify directions for future research. Embedding a deep-learning model in the known structure of cellular systems yields DCell, a ‘visible’ neural network that can be used to mechanistically interpret genotype–phenotype relationships. The broad set of deep generative models (DGMs) has achieved remarkable advances. However, it is often difficult to incorporate rich structured domain knowledge with the end-to-end DGMs. Posterior regularization (PR) offers a principled framework to impose structured constraints on probabilistic models, but has limited applicability to the diverse DGMs that can lack a Bayesian formulation or even explicit density evaluation. PR also requires constraints to be fully specified a priori, which is impractical or suboptimal for complex knowledge with learnable uncertain parts. In this paper, we establish mathematical correspondence between PR and reinforcement learning (RL), and, based on the connection, expand PR to learn constraints as the extrinsic reward in RL. The resulting algorithm is model-agnostic to apply to any DGMs, and is flexible to adapt arbitrary constraints with the model jointly. Experiments on human image generation and templated sentence generation show models with learned knowledge constraints by our algorithm greatly improve over base generative models.