Biological data are extremely diverse, complex but also quite sparse. The recent developments in deep learning methods are offering new possibilities for the analysis of complex data. However, it is easy to be get a deep learning model that seems to have good results but is in fact either overfitting the training data or the validation data. In particular, the fact to overfit the validation data, called "information leak", is almost never treated in papers proposing deep learning models to predict protein-protein interactions (PPI). In this work, we compare two carefully designed deep learning models and show pitfalls to avoid while predicting PPIs through machine learning methods. Our best model predicts accurately more than 78 of human PPI, in very strict conditions both for training and testing. The methodology we propose here allow us to have strong confidences about the ability of a model to scale up on larger datasets. This would allow sharper models when larger datasets would be available, rather than current models prone to information leaks. Our solid methodological foundations shall be applicable to more organisms and whole proteome networks predictions.
proposed in @cite_0 a plain fully connected neural network, similar to our first model in this paper but significantly bigger, with layers containing 512, 256 and 128 units for what should be feature extraction, and 128 units for the head of their network. However, they are not giving as input to the network protein sequences but a list of features, such as sequence-order descriptors and composition-transition-distribution descriptors, that authors extracted themselves. They used an hold-out validation set together with a test set but then switched for a 5-fold cross validation when comparing their model with others on some other datasets.
@cite_0
2139582206 2885583144 2126486632 2526782364
The effect of training a neural network secondary structure prediction algorithm with different types of multiple sequence alignment profiles derived from the same sequences, is shown to provide a range of accuracy from 70.5 to 76.4 . The best accuracy of 76.4 (standard deviation 8.4 ), is 3.1 (Q3) and 4.4 (SOV2) better than the PHD algorithm run on the same set of 406 sequence non-redundant proteins that were not used to train either method. Residues predicted by the new method with a confidence value of 5 or greater, have an average Q3 accuracy of 84 , and cover 68 of the residues. Relative solvent accessibility based on a two state model, for 25, 5, and 0 accessibility are predicted at 76.2, 79.8, and 86.6 accuracy respectively. The source of the improvements obtained from training with different representations of the same alignment data are described in detail. The new Jnet prediction method resulting from this study is available in the Jpred secondary structure prediction server, and as a stand-alone computer program from: http: barton.ebi.ac.uk . Proteins 2000;40:502–511. © 2000 Wiley-Liss, Inc. 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. 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. Recently, neuron activations extracted from a pre-trained convolutional neural network (CNN) show promising performance in various visual tasks. However, due to the domain and task bias, using the features generated from the model pre-trained for image classification as image representations for instance retrieval is problematic. In this paper, we propose quartet-net learning to improve the discriminative power of CNN features for instance retrieval. The general idea is to map the features into a space where the image similarity can be better evaluated. Our network differs from the traditional Siamese-net in two ways. First, we adopt a double-margin contrastive loss with a dynamic margin tuning strategy to train the network which leads to more robust performance. Second, we introduce in the mimic learning regularization to improve the generalization ability of the network by preventing it from overfitting to the training data. Catering for the network learning, we collect a large-scale dataset, namely GeoPair, which consists of 68k matching image pairs and 63k non-matching pairs. Experiments on several standard instance retrieval datasets demonstrate the effectiveness of our method.