scholarly journals PconsC4: fast, free, easy, and accurate contact predictions

2018 ◽  
Author(s):  
Mirco Michel ◽  
David Menéndez Hurtado ◽  
Arne Elofsson
Keyword(s):  
Deep Learning ◽  
State Of The Art ◽  
Prediction Methods ◽  
Coupling Analysis ◽  
Learning Methods ◽  
Contact Prediction ◽  
Residue Contact ◽  
Direct Coupling Analysis ◽  
Computationally Expensive ◽  
Contact Predictions

AbstractMotivationResidue contact prediction was revolutionized recently by the introduction of direct coupling analysis (DCA). Further improvements, in particular for small families, have been obtained by the combination of DCA and deep learning methods. However, existing deep learning contact prediction methods often rely on a number of external programs and are therefore computationally expensive.ResultsHere, we introduce a novel contact predictor, PconsC4, which performs on par with state of the art methods. PconsC4 is heavily optimized, does not use any external programs and therefore is significantly faster and easier to use than other methods.AvailabilityPconsC4 is freely available under the GPL license from https://github.com/ElofssonLab/PconsC4. Installation is easy using the pip command and works on any system with Python 3.5 or later and a modern GCC [email protected]

PconsC4: fast, accurate and hassle-free contact predictions

2018 ◽  
Vol 35 (15) ◽  
pp. 2677-2679 ◽  
Author(s):  
Mirco Michel ◽  
David Menéndez Hurtado ◽  
Arne Elofsson
Keyword(s):  
Deep Learning ◽  
State Of The Art ◽  
Supplementary Information ◽  
Prediction Methods ◽  
Coupling Analysis ◽  
Contact Prediction ◽  
Residue Contact ◽  
Direct Coupling Analysis ◽  
Computationally Expensive ◽  
Contact Predictions

Abstract Motivation Residue contact prediction was revolutionized recently by the introduction of direct coupling analysis (DCA). Further improvements, in particular for small families, have been obtained by the combination of DCA and deep learning methods. However, existing deep learning contact prediction methods often rely on a number of external programs and are therefore computationally expensive. Results Here, we introduce a novel contact predictor, PconsC4, which performs on par with state of the art methods. PconsC4 is heavily optimized, does not use any external programs and therefore is significantly faster and easier to use than other methods. Availability and implementation PconsC4 is freely available under the GPL license from https://github.com/ElofssonLab/PconsC4. Installation is easy using the pip command and works on any system with Python 3.5 or later and a GCC compiler. It does not require a GPU nor special hardware. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Combination of deep neural network with attention mechanism enhances the explainability of protein contact prediction

2020 ◽  
Author(s):  
Chen Chen ◽  
Tianqi Wu ◽  
Zhiye Guo ◽  
Jianlin Cheng
Keyword(s):  
Neural Network ◽  
Deep Learning ◽  
Attention Mechanism ◽  
Contact Prediction ◽  
Residue Contact ◽  
Complementary Effect ◽  
Essential Components ◽  
Internal Mechanism ◽  
Contact Predictions ◽  
The Relationship

AbstractDeep learning has emerged as a revolutionary technology for protein residue-residue contact prediction since the 2012 CASP10 competition. Considerable advancements in the predictive power of the deep learning-based contact predictions have been achieved since then. However, little effort has been put into interpreting the black-box deep learning methods. Algorithms that can interpret the relationship between predicted contact maps and the internal mechanism of the deep learning architectures are needed to explore the essential components of contact inference and improve their explainability. In this study, we present an attention-based convolutional neural network for protein contact prediction, which consists of two attention mechanism-based modules: sequence attention and regional attention. Our benchmark results on the CASP13 free-modeling (FM) targets demonstrate that the two attention modules added on top of existing typical deep learning models exhibit a complementary effect that contributes to predictive improvements. More importantly, the inclusion of the attention mechanism provides interpretable patterns that contain useful insights into the key fold-determining residues in proteins. We expect the attention-based model can provide a reliable and practically interpretable technique that helps break the current bottlenecks in explaining deep neural networks for contact prediction.

scholarly journals Deep learning reveals many more inter-protein residue-residue contacts than direct coupling analysis

2017 ◽  
Author(s):  
Tian-ming Zhou ◽  
Sheng Wang ◽  
Jinbo Xu
Keyword(s):  
Deep Learning ◽  
Protein Interaction ◽  
Interaction Network ◽  
Protein Docking ◽  
Residue Level ◽  
Direct Coupling ◽  
Coupling Analysis ◽  
Multiple Sequence ◽  
Contact Prediction ◽  
Direct Coupling Analysis

AbstractIntra-protein residue-level contact prediction has drawn a lot of attentions in recent years and made very good progress, but much fewer methods are dedicated to inter-protein contact prediction, which are important for understanding how proteins interact at structure and residue level. Direct coupling analysis (DCA) is popular for intra-protein contact prediction, but extending it to inter-protein contact prediction is challenging since it requires too many interlogs (i.e., interacting homologs) to be effective, which cannot be easily fulfilled especially for a putative interacting protein pair in eukaryotes. We show that deep learning, even trained by only intra-protein contact maps, works much better than DCA for inter-protein contact prediction. We also show that a phylogeny-based method can generate a better multiple sequence alignment for eukaryotes than existing genome-based methods and thus, lead to better inter-protein contact prediction. Our method shall be useful for protein docking, protein interaction prediction and protein interaction network construction.

scholarly journals Learning Feature Interactions with Lorentzian Factorization Machine

2020 ◽  
Vol 34 (04) ◽  
pp. 6470-6477
Author(s):  
Canran Xu ◽  
Ming Wu
Keyword(s):  
Deep Learning ◽  
Hyperbolic Space ◽  
Recommendation System ◽  
Triangle Inequality ◽  
State Of The Art ◽  
Learning Methods ◽  
New Model ◽  
User Behaviors ◽  
Feature Interactions ◽  
Factorization Machine

Learning representations for feature interactions to model user behaviors is critical for recommendation system and click-trough rate (CTR) predictions. Recent advances in this area are empowered by deep learning methods which could learn sophisticated feature interactions and achieve the state-of-the-art result in an end-to-end manner. These approaches require large number of training parameters integrated with the low-level representations, and thus are memory and computational inefficient. In this paper, we propose a new model named “LorentzFM” that can learn feature interactions embedded in a hyperbolic space in which the violation of triangle inequality for Lorentz distances is available. To this end, the learned representation is benefited by the peculiar geometric properties of hyperbolic triangles, and result in a significant reduction in the number of parameters (20% to 80%) because all the top deep learning layers are not required. With such a lightweight architecture, LorentzFM achieves comparable and even materially better results than the deep learning methods such as DeepFM, xDeepFM and Deep & Cross in both recommendation and CTR prediction tasks.

scholarly journals Single-Cell Phenotype Classification Using Deep Convolutional Neural Networks

2016 ◽  
Vol 21 (9) ◽  
pp. 998-1003 ◽  
Author(s):  
Oliver Dürr ◽  
Beate Sick
Keyword(s):  
Machine Learning ◽  
Neural Networks ◽  
Deep Learning ◽  
Single Cell ◽  
Convolutional Neural Networks ◽  
State Of The Art ◽  
Misclassification Rate ◽  
Support Vector ◽  
Learning Methods ◽  
Phenotype Classification

Deep learning methods are currently outperforming traditional state-of-the-art computer vision algorithms in diverse applications and recently even surpassed human performance in object recognition. Here we demonstrate the potential of deep learning methods to high-content screening–based phenotype classification. We trained a deep learning classifier in the form of convolutional neural networks with approximately 40,000 publicly available single-cell images from samples treated with compounds from four classes known to lead to different phenotypes. The input data consisted of multichannel images. The construction of appropriate feature definitions was part of the training and carried out by the convolutional network, without the need for expert knowledge or handcrafted features. We compare our results against the recent state-of-the-art pipeline in which predefined features are extracted from each cell using specialized software and then fed into various machine learning algorithms (support vector machine, Fisher linear discriminant, random forest) for classification. The performance of all classification approaches is evaluated on an untouched test image set with known phenotype classes. Compared to the best reference machine learning algorithm, the misclassification rate is reduced from 8.9% to 6.6%.

scholarly journals Phylogenetic correlations have limited effect on coevolution-based contact prediction in proteins

2020 ◽  
Author(s):  
Edwin Rodriguez Horta ◽  
Martin Weigt
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Protein Sequences ◽  
Protein Families ◽  
Coupling Analysis ◽  
Contact Prediction ◽  
Phylogenetic Relations ◽  
Direct Coupling Analysis

AbstractCoevolution-based contact prediction, either directly by coevolutionary couplings resulting from global statistical sequence models or using structural supervision and deep learning, has found widespread application in protein-structure prediction from sequence. However, one of the basic assumptions in global statistical modeling is that sequences form an at least approximately independent sample of an unknown probability distribution, which is to be learned from data. In the case of protein families, this assumption is obviously violated by phylogenetic relations between protein sequences. It has turned out to be notoriously difficult to take phylogenetic correlations into account in coevolutionary model learning. Here, we propose a complementary approach: we develop two strategies to randomize or resample sequence data, such that conservation patterns and phylogenetic relations are preserved, while intrinsic (i.e. structure- or function-based) coevolutionary couplings are removed. An analysis of these data shows that the strongest coevolutionary couplings, i.e. those used by Direct Coupling Analysis to predict contacts, are only weakly influenced by phylogeny. However, phylogeny-induced spurious couplings are of similar size to the bulk of coevolutionary couplings, and dissecting functional from phylogeny-induced couplings might lead to more accurate contact predictions in the range of intermediate-size couplings.The code is available at https://github.com/ed-rodh/Null_models_I_and_II.Author summaryMany homologous protein families contain thousands of highly diverged amino-acid sequences, which fold in close-to-identical three-dimensional structures and fulfill almost identical biological tasks. Global coevolutionary models, like those inferred by the Direct Coupling Analysis (DCA), assume that families can be considered as samples of some unknown statistical model, and that the parameters of these models represent evolutionary constraints acting on protein sequences. To learn these models from data, DCA and related approaches have to also assume that the distinct sequences in a protein family are close to independent, while in reality they are characterized by involved hierarchical phylogenetic relationships. Here we propose Null models for sequence alignments, which maintain patterns of amino-acid conservation and phylogeny contained in the data, but destroy any coevolutionary couplings, frequently used in protein structure prediction. We find that phylogeny actually induces spurious non-zero couplings. These are, however, significantly smaller that the largest couplings derived from natural sequences, and therefore have only little influence on the first predicted contacts. However, in the range of intermediate couplings, they may lead to statistically significant effects. Dissecting phylogenetic from functional couplings might therefore extend the range of accurately predicted structural contacts down to smaller coupling strengths than those currently used.

scholarly journals Accurate contact-based modelling of repeat proteins predicts the structure of new repeats protein families

2021 ◽  
Vol 17 (4) ◽  
pp. e1008798
Author(s):  
Claudio Bassot ◽  
Arne Elofsson
Keyword(s):  
Deep Learning ◽  
Protein Structure ◽  
High Accuracy ◽  
Unique Sequence ◽  
Direct Coupling ◽  
Protein Families ◽  
Coupling Analysis ◽  
Repeat Proteins ◽  
Eukaryotic Proteomes ◽  
Direct Coupling Analysis

Repeat proteins are abundant in eukaryotic proteomes. They are involved in many eukaryotic specific functions, including signalling. For many of these proteins, the structure is not known, as they are difficult to crystallise. Today, using direct coupling analysis and deep learning it is often possible to predict a protein’s structure. However, the unique sequence features present in repeat proteins have been a challenge to use direct coupling analysis for predicting contacts. Here, we show that deep learning-based methods (trRosetta, DeepMetaPsicov (DMP) and PconsC4) overcomes this problem and can predict intra- and inter-unit contacts in repeat proteins. In a benchmark dataset of 815 repeat proteins, about 90% can be correctly modelled. Further, among 48 PFAM families lacking a protein structure, we produce models of forty-one families with estimated high accuracy.

scholarly journals FilterDCA: interpretable supervised contact prediction using inter-domain coevolution

2019 ◽  
Author(s):  
Maureen Muscat ◽  
Giancarlo Croce ◽  
Edoardo Sarti ◽  
Martin Weigt
Keyword(s):  
Deep Learning ◽  
De Novo ◽  
Protein Complexes ◽  
Protein Structures ◽  
Direct Coupling ◽  
Sequence Information ◽  
Coupling Analysis ◽  
Contact Patterns ◽  
Direct Coupling Analysis ◽  
Training Sets

AbstractPredicting three-dimensional protein structure and assembling protein complexes using sequence information belongs to the most prominent tasks in computational biology. Recently substantial progress has been obtained in the case of single proteins using a combination of unsupervised coevolutionary sequence analysis with structurally supervised deep learning. While reaching impressive accuracies in predicting residue-residue contacts, deep learning has a number of disadvantages. The need for large structural training sets limits the applicability to multi-protein complexes; and their deep architecture makes the interpretability of the convolutional neural networks intrinsically hard. Here we introduce FilterDCA, a simpler supervised predictor for inter-domain and inter-protein contacts. It is based on the fact that contact maps of proteins show typical contact patterns, which results from secondary structure and are reflected by patterns in coevolutionary analysis. We explicitly integrate averaged contacts patterns with coevolutionary scores derived by Direct Coupling Analysis, reaching results comparable to more complex deep-learning approaches, while remaining fully transparent and interpretable. The FilterDCA code is available at http://gitlab.lcqb.upmc.fr/muscat/FilterDCA.Author summaryThe de novo prediction of tertiary and quaternary protein structures has recently seen important advances, by combining unsupervised, purely sequence-based coevolutionary analyses with structure-based supervision using deep learning for contact-map prediction. While showing impressive performance, deep-learning methods require large training sets and pose severe obstacles for their interpretability. Here we construct a simple, transparent and therefore fully interpretable inter-domain contact predictor, which uses the results of coevolutionary Direct Coupling Analysis in combination with explicitly constructed filters reflecting typical contact patterns in a training set of known protein structures, and which improves the accuracy of predicted contacts significantly. Our approach thereby sheds light on the question how contact information is encoded in coevolutionary signals.

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