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
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A variety of functionally important protein properties, such as secondary structure, transmembrane topology and solvent accessibility, can be encoded as a labeling of amino acids. Indeed, the prediction of such properties from the primary amino acid sequence is one of the core projects of computational biology. Accordingly, a panoply of approaches have been developed for predicting such properties; however, most such approaches focus on solving a single task at a time. Motivated by recent, successful work in natural language processing, we propose to use multitask learning to train a single, joint model that exploits the dependencies among these various labeling tasks. We describe a deep neural network architecture that, given a protein sequence, outputs a host of predicted local properties, including secondary structure, solvent accessibility, transmembrane topology, signal peptides and DNA-binding residues. The network is trained jointly on all these tasks in a supervised fashion, augmented with a novel form of semi-supervised learning in which the model is trained to distinguish between local patterns from natural and synthetic protein sequences. The task-independent architecture of the network obviates the need for task-specific feature engineering. We demonstrate that, for all of the tasks that we considered, our approach leads to statistically significant improvements in performance, relative to a single task neural network approach, and that the resulting model achieves state-of-the-art performance. In human learning, it is common to use multiple sources of information jointly. However, most existing feature learning approaches learn from only a single task. In this paper, we propose a novel multi-task deep network to learn generalizable high-level visual representations. Since multitask learning requires annotations for multiple properties of the same training instance, we look to synthetic images to train our network. To overcome the domain difference between real and synthetic data, we employ an unsupervised feature space domain adaptation method based on adversarial learning. Given an input synthetic RGB image, our network simultaneously predicts its surface normal, depth, and instance contour, while also minimizing the feature space domain differences between real and synthetic data. Through extensive experiments, we demonstrate that our network learns more transferable representations compared to single-task baselines. Our learned representation produces state-of-the-art transfer learning results on PASCAL VOC 2007 classification and 2012 detection. We present a deep learning approach for high resolution face completion with multiple controllable attributes (e.g., male and smiling) under arbitrary masks. Face completion entails understanding both structural meaningfulness and appearance consistency locally and globally to fill in "holes" whose content do not appear elsewhere in an input image. It is a challenging task with the difficulty level increasing significantly with respect to high resolution, the complexity of "holes" and the controllable attributes of filled-in fragments. Our system addresses the challenges by learning a fully end-to-end framework that trains generative adversarial networks (GANs) progressively from low resolution to high resolution with conditional vectors encoding controllable attributes. We design novel network architectures to exploit information across multiple scales effectively and efficiently. We introduce new loss functions encouraging sharp completion. We show that our system can complete faces with large structural and appearance variations using a single feed-forward pass of computation with mean inference time of 0.007 seconds for images at 1024 x 1024 resolution. We also perform a pilot human study that shows our approach outperforms state-of-the-art face completion methods in terms of rank analysis. The code will be released upon publication. Machine learning based predictions of protein–protein interactions (PPIs) could provide valuable insights into protein functions, disease occurrence, and therapy design on a large scale. The intensive feature engineering in most of these methods makes the prediction task more tedious and trivial. The emerging deep learning technology enabling automatic feature engineering is gaining great success in various fields. However, the over-fitting and generalization of its models are not yet well investigated in most scenarios. Here, we present a deep neural network framework (DNN-PPI) for predicting PPIs using features learned automatically only from protein primary sequences. Within the framework, the sequences of two interacting proteins are sequentially fed into the encoding, embedding, convolution neural network (CNN), and long short-term memory (LSTM) neural network layers. Then, a concatenated vector of the two outputs from the previous layer is wired as the input of the fully connected neural network. Finally, the Adam optimizer is applied to learn the network weights in a back-propagation fashion. The different types of features, including semantic associations between amino acids, position-related sequence segments (motif), and their long- and short-term dependencies, are captured in the embedding, CNN and LSTM layers, respectively. When the model was trained on Pan’s human PPI dataset, it achieved a prediction accuracy of 98.78 at the Matthew’s correlation coefficient (MCC) of 97.57 . The prediction accuracies for six external datasets ranged from 92.80 to 97.89 , making them superior to those achieved with previous methods. When performed on Escherichia coli, Drosophila, and Caenorhabditis elegans datasets, DNN-PPI obtained prediction accuracies of 95.949 , 98.389 , and 98.669 , respectively. The performances in cross-species testing among the four species above coincided in their evolutionary distances. However, when testing Mus Musculus using the models from those species, they all obtained prediction accuracies of over 92.43 , which is difficult to achieve and worthy of note for further study. These results suggest that DNN-PPI has remarkable generalization and is a promising tool for identifying protein interactions.