Protein secondary structure (SS) prediction is important for studying protein structure and function. When only the sequence (profile) information is used as input feature, currently the best ...predictors can obtain ~80% Q3 accuracy, which has not been improved in the past decade. Here we present DeepCNF (Deep Convolutional Neural Fields) for protein SS prediction. DeepCNF is a Deep Learning extension of Conditional Neural Fields (CNF), which is an integration of Conditional Random Fields (CRF) and shallow neural networks. DeepCNF can model not only complex sequence-structure relationship by a deep hierarchical architecture, but also interdependency between adjacent SS labels, so it is much more powerful than CNF. Experimental results show that DeepCNF can obtain ~84% Q3 accuracy, ~85% SOV score, and ~72% Q8 accuracy, respectively, on the CASP and CAMEO test proteins, greatly outperforming currently popular predictors. As a general framework, DeepCNF can be used to predict other protein structure properties such as contact number, disorder regions, and solvent accessibility.
Bayesian networks can capture causal relations, but learning such a network from data is NP-hard. Recent work has made it possible to approximate this problem as a continuous optimization task that ...can be solved efficiently with well-established numerical techniques.
Although artificial neural networks are powerful classifiers, their internal structures are hard to interpret. In the life sciences, extensive knowledge of cell biology provides an opportunity to ...design visible neural networks (VNNs) that couple the model's inner workings to those of real systems. Here we develop DCell, a VNN embedded in the hierarchical structure of 2,526 subsystems comprising a eukaryotic cell (http://d-cell.ucsd.edu/). Trained on several million genotypes, DCell simulates cellular growth nearly as accurately as laboratory observations. During simulation, genotypes induce patterns of subsystem activities, enabling in silico investigations of the molecular mechanisms underlying genotype-phenotype associations. These mechanisms can be validated, and many are unexpected; some are governed by Boolean logic. Cumulatively, 80% of the importance for growth prediction is captured by 484 subsystems (21%), reflecting the emergence of a complex phenotype. DCell provides a foundation for decoding the genetics of disease, drug resistance and synthetic life.
Template-based modeling, including homology modeling and protein threading, is the most reliable method for protein 3D structure prediction. However, alignment errors and template selection are still ...the main bottleneck for current template-base modeling methods, especially when proteins under consideration are distantly related.
We present a novel context-specific alignment potential for protein threading, including alignment and template selection. Our alignment potential measures the log-odds ratio of one alignment being generated from two related proteins to being generated from two unrelated proteins, by integrating both local and global context-specific information. The local alignment potential quantifies how well one sequence residue can be aligned to one template residue based on context-specific information of the residues. The global alignment potential quantifies how well two sequence residues can be placed into two template positions at a given distance, again based on context-specific information. By accounting for correlation among a variety of protein features and making use of context-specific information, our alignment potential is much more sensitive than the widely used context-independent or profile-based scoring function. Experimental results confirm that our method generates significantly better alignments and threading results than the best profile-based methods on several large benchmarks. Our method works particularly well for distantly related proteins or proteins with sparse sequence profiles because of the effective integration of context-specific, structure and global information.
http://raptorx.uchicago.edu/download/.
Protein structure alignment is a fundamental problem in computational structure biology. Many programs have been developed for automatic protein structure alignment, but most of them align two ...protein structures purely based upon geometric similarity without considering evolutionary and functional relationship. As such, these programs may generate structure alignments which are not very biologically meaningful from the evolutionary perspective. This paper presents a novel method DeepAlign for automatic pairwise protein structure alignment. DeepAlign aligns two protein structures using not only spatial proximity of equivalent residues (after rigid-body superposition), but also evolutionary relationship and hydrogen-bonding similarity. Experimental results show that DeepAlign can generate structure alignments much more consistent with manually-curated alignments than other automatic tools especially when proteins under consideration are remote homologs. These results imply that in addition to geometric similarity, evolutionary information and hydrogen-bonding similarity are essential to aligning two protein structures.
Intrinsically disordered proteins or protein regions are involved in key biological processes including regulation of transcription, signal transduction, and alternative splicing. Accurately ...predicting order/disorder regions ab initio from the protein sequence is a prerequisite step for further analysis of functions and mechanisms for these disordered regions. This work presents a learning method, weighted DeepCNF (Deep Convolutional Neural Fields), to improve the accuracy of order/disorder prediction by exploiting the long-range sequential information and the interdependency between adjacent order/disorder labels and by assigning different weights for each label during training and prediction to solve the label imbalance issue. Evaluated by the CASP9 and CASP10 targets, our method obtains 0.855 and 0.898 AUC values, which are higher than the state-of-the-art single ab initio predictors.
Sequence-based protein homology detection has been extensively studied and so far the most sensitive method is based upon comparison of protein sequence profiles, which are derived from multiple ...sequence alignment (MSA) of sequence homologs in a protein family. A sequence profile is usually represented as a position-specific scoring matrix (PSSM) or an HMM (Hidden Markov Model) and accordingly PSSM-PSSM or HMM-HMM comparison is used for homolog detection. This paper presents a new homology detection method MRFalign, consisting of three key components: 1) a Markov Random Fields (MRF) representation of a protein family; 2) a scoring function measuring similarity of two MRFs; and 3) an efficient ADMM (Alternating Direction Method of Multipliers) algorithm aligning two MRFs. Compared to HMM that can only model very short-range residue correlation, MRFs can model long-range residue interaction pattern and thus, encode information for the global 3D structure of a protein family. Consequently, MRF-MRF comparison for remote homology detection shall be much more sensitive than HMM-HMM or PSSM-PSSM comparison. Experiments confirm that MRFalign outperforms several popular HMM or PSSM-based methods in terms of both alignment accuracy and remote homology detection and that MRFalign works particularly well for mainly beta proteins. For example, tested on the benchmark SCOP40 (8353 proteins) for homology detection, PSSM-PSSM and HMM-HMM succeed on 48% and 52% of proteins, respectively, at superfamily level, and on 15% and 27% of proteins, respectively, at fold level. In contrast, MRFalign succeeds on 57.3% and 42.5% of proteins at superfamily and fold level, respectively. This study implies that long-range residue interaction patterns are very helpful for sequence-based homology detection. The software is available for download at http://raptorx.uchicago.edu/download/. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.
In this paper, we propose AirSign, a novel user authentication technology to provide users with more convenient, intuitive, and secure ways of interacting with smartphones in daily settings. AirSign ...leverages both acoustic and motion sensors for user authentication by signing signatures in the air through smartphones without requiring any special hardware. This technology actively transmits inaudible acoustic signals from the earpiece speaker, receives echoes back through both built-in microphones to "illuminate" signature and hand geometry, and authenticates users according to the unique features extracted from echoes and motion sensors. To evaluate our system, we collected registered, genuine, and forged signatures from 30 participants, and by applying AirSign on the above dataset, we were able to successfully distinguish between genuine and forged signatures with a 97.1% F-score while requesting only seven signatures during the registration phase.
Diffractive optical neural networks (DONNs) are emerging as high‐throughput and energy‐efficient hardware platforms to perform all‐optical machine learning (ML) in machine vision systems. However, ...the current demonstrated applications of DONNs are largely image classification tasks, which undermine the prospect of developing and utilizing such hardware for other ML applications. Herein, the deployment of an all‐optical reconfigurable DONNs system for scientific computing is demonstrated numerically and experimentally, including guiding two‐dimensional quantum material synthesis, predicting the properties of two‐dimensional quantum materials and small molecular cancer drugs, predicting the device response of nanopatterned integrated photonic power splitters, and the dynamic stabilization of an inverted pendulum with reinforcement learning. Despite a large variety of input data structures, a universal feature engineering approach is developed to convert categorical input features to images that can be processed in the DONNs system. The results open up new opportunities for employing DONNs systems for a broad range of ML applications.
An all‐optical reconfigurable diffractive optical neural network system is deployed for performing scientific computing tasks, including guiding two‐dimensional quantum material synthesis, predicting the properties of two‐dimensional quantum materials and small molecular cancer drugs, predicting the device response of nanopatterned‐integrated photonic power splitters, and the dynamic stabilization of an inverted pendulum with reinforcement learning.
It is hard to directly deploy deep learning models on today’s smartphones due to the substantial computational costs introduced by millions of parameters. To compress the model, we develop an ...ℓ0-based sparse group lasso model called MobilePrune which can generate extremely compact neural network models for both desktop and mobile platforms. We adopt group lasso penalty to enforce sparsity at the group level to benefit General Matrix Multiply (GEMM) and develop the very first algorithm that can optimize the ℓ0 norm in an exact manner and achieve the global convergence guarantee in the deep learning context. MobilePrune also allows complicated group structures to be applied on the group penalty (i.e., trees and overlapping groups) to suit DNN models with more complex architectures. Empirically, we observe the substantial reduction of compression ratio and computational costs for various popular deep learning models on multiple benchmark datasets compared to the state-of-the-art methods. More importantly, the compression models are deployed on the android system to confirm that our approach is able to achieve less response delay and battery consumption on mobile phones.
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