PredMP: a web server for de novo prediction and visualization of membrane proteins

AbstractMotivationDe novo peptide sequencing based on tandem mass spectrometry data is the key technology of shotgun proteomics for identifying peptides without any database and assembling unknown proteins. However, owing to the low ion coverage in tandem mass spectra, the order of certain consecutive amino acids cannot be determined if all of their supporting fragment ions are missing, which results in the low precision of de novo sequencing.ResultsIn order to solve this problem, we developed pNovo 3, which used a learning-to-rank framework to distinguish similar peptide candidates for each spectrum. Three metrics for measuring the similarity between each experimental spectrum and its corresponding theoretical spectrum were used as important features, in which the theoretical spectra can be precisely predicted by the pDeep algorithm using deep learning. On seven benchmark datasets from six diverse species, pNovo 3 recalled 29–102% more correct spectra, and the precision was 11–89% higher than three other state-of-the-art de novo sequencing algorithms. Furthermore, compared with the newly developed DeepNovo, which also used the deep learning approach, pNovo 3 still identified 21–50% more spectra on the nine datasets used in the study of DeepNovo. In summary, the deep learning and learning-to-rank techniques implemented in pNovo 3 significantly improve the precision of de novo sequencing, and such machine learning framework is worth extending to other related research fields to distinguish the similar sequences.Availability and implementationpNovo 3 can be freely downloaded from http://pfind.ict.ac.cn/software/pNovo/index.html.Supplementary informationSupplementary data are available at Bioinformatics online.

Download Full-text

Personalized deep learning of individual immunopeptidomes to identify neoantigens for cancer vaccines

10.1101/620468 ◽

2019 ◽

Cited By ~ 1

Author(s):

Ngoc Hieu Tran ◽

Rui Qiao ◽

Lei Xin ◽

Xin Chen ◽

Baozhen Shan ◽

...

Keyword(s):

Mass Spectrometry ◽

Deep Learning ◽

De Novo ◽

Mass Spectrometry Data ◽

Main Role ◽

Accurate Identification ◽

Identification Rate ◽

Cell Responses ◽

First Time ◽

Deep Learning Model

AbstractTumor-specific neoantigens play the main role for developing personal vaccines in cancer immunotherapy. We propose, for the first time, a personalized de novo sequencing workflow to identify HLA-I and HLA-II neoantigens directly and solely from mass spectrometry data. Our workflow trains a personal deep learning model on the immunopeptidome of an individual patient and then uses it to predict mutated neoantigens of that patient. This personalized learning and mass spectrometry-based approach enables comprehensive and accurate identification of neoantigens. We applied the workflow to datasets of five melanoma patients and substantially improved the accuracy and identification rate of de novo HLA peptides by 14.3% and 38.9%, respectively. This subsequently led to the identification of 10,440 HLA-I and 1,585 HLA-II new peptides that were not presented in existing databases. Most importantly, our workflow successfully discovered 17 neoantigens of both HLA-I and HLA-II, including those with validated T cell responses and those novel neoantigens that had not been reported in previous studies.

Download Full-text

DrugEx v2: De Novo Design of Drug Molecule by Pareto-based Multi-Objective Reinforcement Learning in Polypharmacology

10.26434/chemrxiv.14474127 ◽

2021 ◽

Author(s):

Xuhan Liu ◽

Kai Ye ◽

Herman Van Vlijmen ◽

Michael T. M. Emmerich ◽

Adriaan P. IJzerman ◽

...

Keyword(s):

Deep Learning ◽

Reinforcement Learning ◽

Drug Target ◽

De Novo ◽

Multi Objective ◽

Learning Framework ◽

Drug Molecules ◽

Pareto Ranking ◽

Speed Up ◽

Deep Learning Model

In polypharmacology, ideal drugs are required to bind to multiple specific targets to enhance efficacy or to reduce resistance formation. Although deep learning has achieved breakthrough in drug discovery, most of its applications only focus on a single drug target to generate drug-like active molecules in spite of the reality that drug molecules often interact with more than one target which can have desired (polypharmacology) or undesired (toxicity) effects. In a previous study we proposed a new method named DrugEx that integrates an exploration strategy into RNN-based reinforcement learning to improve the diversity of the generated molecules. Here, we extended our DrugEx algorithm with multi-objective optimization to generate drug molecules towards more than one specific target (two adenosine receptors, A1AR and A2AAR, and the potassium ion channel hERG in this study). In our model, we applied an RNN as the agent and machine learning predictors as the environment, both of which were pre-trained in advance and then interplayed under the reinforcement learning framework. The concept of evolutionary algorithms was merged into our method such that crossover and mutation operations were implemented by the same deep learning model as the agent. During the training loop, the agent generates a batch of SMILES-based molecules. Subsequently scores for all objectives provided by the environment are used for constructing Pareto ranks of the generated molecules with non-dominated sorting and Tanimoto-based crowding distance algorithms. Here, we adopted GPU acceleration to speed up the process of Pareto optimization. The final reward of each molecule is calculated based on the Pareto ranking with the ranking selection algorithm. The agent is trained under the guidance of the reward to make sure it can generate more desired molecules after convergence of the training process. All in all we demonstrate generation of compounds with a diverse predicted selectivity profile toward multiple targets, offering the potential of high efficacy and lower toxicity.

Download Full-text

A Deep Learning Model Generation Framework for Virtualized Multi-Access Edge Cache Management

IEEE Access ◽

10.1109/access.2019.2916080 ◽

2019 ◽

Vol 7 ◽

pp. 62734-62749 ◽

Cited By ~ 8

Author(s):

Kyi Thar ◽

Thant Zin Oo ◽

Yan Kyaw Tun ◽

Do Hyeon Kim ◽

Ki Tae Kim ◽

...

Keyword(s):

Deep Learning ◽

Learning Model ◽

Model Generation ◽

Cache Management ◽

Multi Access ◽

Deep Learning Model

Download Full-text

How to Generate Image Dataset based on 3D Model and Deep Learning Method

International Journal of Engineering & Technology ◽

10.14419/ijet.v7i3.34.18969 ◽

2018 ◽

Vol 7 (3.34) ◽

pp. 221

Author(s):

Sooyoung Cho ◽

Sang Geun Choi ◽

Daeyeol Kim ◽

Gyunghak Lee ◽

Chae BongSohn

Keyword(s):

Computer Vision ◽

Deep Learning ◽

Object Recognition ◽

Object Tracking ◽

3D Model ◽

Object Segmentation ◽

Learning Method ◽

Data Set ◽

Image Dataset ◽

Deep Learning Model

Performances of computer vision tasks have been drastically improved after applying deep learning. Such object recognition, object segmentation, object tracking, and others have been approached to the super-human level. Most of the algorithms were trained by using supervised learning. In general, the performance of computer vision is improved by increasing the size of the data. The collected data was labeled and used as a data set of the YOLO algorithm. In this paper, we propose a data set generation method using Unity which is one of the 3D engines. The proposed method makes it easy to obtain the data necessary for learning. We classify 2D polymorphic objects and test them against various data using a deep learning model. In the classification using CNN and VGG-16, 90% accuracy was achieved. And we used Tiny-YOLO of YOLO algorithm for object recognition and we achieved 78% accuracy. Finally, we compared in terms of virtual and real environments it showed a result of 97 to 99 percent for each accuracy.

Download Full-text

Full-length de novo protein structure determination from cryo-EM maps using deep learning

10.1101/2020.08.28.271981 ◽

2020 ◽

Author(s):

Jiahua He ◽

Sheng-You Huang

Keyword(s):

Deep Learning ◽

Structure Determination ◽

De Novo ◽

Protein Structures ◽

Protein Structure Determination ◽

Full Length ◽

Supplementary Information ◽

General Applicability ◽

Data Set ◽

Convolutional Networks

AbstractAdvances in microscopy instruments and image processing algorithms have led to an increasing number of cryo-EM maps. However, building accurate models for the EM maps at 3-5 Å resolution remains a challenging and time-consuming process. With the rapid growth of deposited EM maps, there is an increasing gap between the maps and reconstructed/modeled 3-dimensional (3D) structures. Therefore, automatic reconstruction of atomic-accuracy full-atom structures from EM maps is pressingly needed. Here, we present a semi-automatic de novo structure determination method using a deep learning-based framework, named as DeepMM, which builds atomic-accuracy all-atom models from cryo-EM maps at near-atomic resolution. In our method, the main-chain and Cα positions as well as their amino acid and secondary structure types are predicted in the EM map using Densely Connected Convolutional Networks. DeepMM was extensively validated on 40 simulated maps at 5 Å resolution and 30 experimental maps at 2.6-4.8 Å resolution as well as an EMDB-wide data set of 2931 experimental maps at 2.6-4.9 Å resolution, and compared with state-of-the-art algorithms including RosettaES, MAINMAST, and Phenix. Overall, our DeepMM algorithm obtained a significant improvement over existing methods in terms of both accuracy and coverage in building full-length protein structures on all test sets, demonstrating the efficacy and general applicability of DeepMM.Availabilityhttps://github.com/JiahuaHe/DeepMMSupplementary informationSupplementary data are available.

Download Full-text

DrugEx v2: De Novo Design of Drug Molecule by Pareto-based Multi-Objective Reinforcement Learning in Polypharmacology

10.26434/chemrxiv.14474127.v1 ◽

2021 ◽

Author(s):

Xuhan Liu ◽

Kai Ye ◽

Herman Van Vlijmen ◽

Michael T. M. Emmerich ◽

Adriaan P. IJzerman ◽

...

Keyword(s):

Deep Learning ◽

Reinforcement Learning ◽

Drug Target ◽

De Novo ◽

Multi Objective ◽

Learning Framework ◽

Drug Molecules ◽

Pareto Ranking ◽

Speed Up ◽

Deep Learning Model

In polypharmacology, ideal drugs are required to bind to multiple specific targets to enhance efficacy or to reduce resistance formation. Although deep learning has achieved breakthrough in drug discovery, most of its applications only focus on a single drug target to generate drug-like active molecules in spite of the reality that drug molecules often interact with more than one target which can have desired (polypharmacology) or undesired (toxicity) effects. In a previous study we proposed a new method named DrugEx that integrates an exploration strategy into RNN-based reinforcement learning to improve the diversity of the generated molecules. Here, we extended our DrugEx algorithm with multi-objective optimization to generate drug molecules towards more than one specific target (two adenosine receptors, A1AR and A2AAR, and the potassium ion channel hERG in this study). In our model, we applied an RNN as the agent and machine learning predictors as the environment, both of which were pre-trained in advance and then interplayed under the reinforcement learning framework. The concept of evolutionary algorithms was merged into our method such that crossover and mutation operations were implemented by the same deep learning model as the agent. During the training loop, the agent generates a batch of SMILES-based molecules. Subsequently scores for all objectives provided by the environment are used for constructing Pareto ranks of the generated molecules with non-dominated sorting and Tanimoto-based crowding distance algorithms. Here, we adopted GPU acceleration to speed up the process of Pareto optimization. The final reward of each molecule is calculated based on the Pareto ranking with the ranking selection algorithm. The agent is trained under the guidance of the reward to make sure it can generate more desired molecules after convergence of the training process. All in all we demonstrate generation of compounds with a diverse predicted selectivity profile toward multiple targets, offering the potential of high efficacy and lower toxicity.

Download Full-text

DrugEx v2: De Novo Design of Drug Molecule by Pareto-based Multi-Objective Reinforcement Learning in Polypharmacology

10.26434/chemrxiv.14474127.v2 ◽

2021 ◽

Author(s):

Xuhan Liu ◽

Kai Ye ◽

Herman Van Vlijmen ◽

Michael T. M. Emmerich ◽

Adriaan P. IJzerman ◽

...

Keyword(s):

Deep Learning ◽

Reinforcement Learning ◽

Drug Target ◽

De Novo ◽

Multi Objective ◽

Learning Framework ◽

Drug Molecules ◽

Pareto Ranking ◽

Speed Up ◽

Deep Learning Model

In polypharmacology, ideal drugs are required to bind to multiple specific targets to enhance efficacy or to reduce resistance formation. Although deep learning has achieved breakthrough in drug discovery, most of its applications only focus on a single drug target to generate drug-like active molecules in spite of the reality that drug molecules often interact with more than one target which can have desired (polypharmacology) or undesired (toxicity) effects. In a previous study we proposed a new method named DrugEx that integrates an exploration strategy into RNN-based reinforcement learning to improve the diversity of the generated molecules. Here, we extended our DrugEx algorithm with multi-objective optimization to generate drug molecules towards more than one specific target (two adenosine receptors, A1AR and A2AAR, and the potassium ion channel hERG in this study). In our model, we applied an RNN as the agent and machine learning predictors as the environment, both of which were pre-trained in advance and then interplayed under the reinforcement learning framework. The concept of evolutionary algorithms was merged into our method such that crossover and mutation operations were implemented by the same deep learning model as the agent. During the training loop, the agent generates a batch of SMILES-based molecules. Subsequently scores for all objectives provided by the environment are used for constructing Pareto ranks of the generated molecules with non-dominated sorting and Tanimoto-based crowding distance algorithms. Here, we adopted GPU acceleration to speed up the process of Pareto optimization. The final reward of each molecule is calculated based on the Pareto ranking with the ranking selection algorithm. The agent is trained under the guidance of the reward to make sure it can generate more desired molecules after convergence of the training process. All in all we demonstrate generation of compounds with a diverse predicted selectivity profile toward multiple targets, offering the potential of high efficacy and lower toxicity.

Download Full-text

Helixer: Cross-species gene annotation of large eukaryotic genomes using deep learning

Bioinformatics ◽

10.1093/bioinformatics/btaa1044 ◽

2020 ◽

Author(s):

Felix Stiehler ◽

Marvin Steinborn ◽

Stephan Scholz ◽

Daniela Dey ◽

Andreas P M Weber ◽

...

Keyword(s):

Deep Learning ◽

De Novo ◽

State Of The Art ◽

Gene Annotation ◽

Land Plant ◽

Supplementary Information ◽

Current State ◽

Learning Capabilities ◽

Vertebrate Model ◽

Eukaryotic Genomes

Abstract Motivation Current state-of-the-art tools for the de novo annotation of genes in eukaryotic genomes have to be specifically fitted for each species and still often produce annotations that can be improved much further. The fundamental algorithmic architecture for these tools has remained largely unchanged for about two decades, limiting learning capabilities. Here, we set out to improve the cross-species annotation of genes from DNA sequence alone with the help of deep learning. The goal is to eliminate the dependency on a closely related gene model while also improving the predictive quality in general with a fundamentally new architecture. Results We present Helixer, a framework for the development and usage of a cross-species deep learning model that improves significantly on performance and generalizability when compared to more traditional methods. We evaluate our approach by building a single vertebrate model for the base-wise annotation of 186 animal genomes and a separate land plant model for 51 plant genomes. Our predictions are shown to be much less sensitive to the length of the genome than those of a current state-of-the-art tool. We also present two novel post-processing techniques that each worked to further strengthen our annotations and show in-depth results of an RNA-Seq based comparison of our predictions. Our method does not yet produce comprehensive gene models but rather outputs base pair wise probabilities. Availability The source code of this work is available at https://github.com/weberlab-hhu/Helixer under the GNU General Public License v3.0. The trained models are available at https://doi.org/10.5281/zenodo.3974409 Supplementary information Supplementary data are available at Bioinformatics online.

Download Full-text

Structure-Based De Novo Molecular Generator Combined with Artificial Intelligence and Docking Simulations

10.26434/chemrxiv.14371967.v1 ◽

2021 ◽

Author(s):

Biao Ma ◽

Kei Terayama ◽

Shigeyuki Matsumoto ◽

Yuta Isaka ◽

Yoko Sasakura ◽

...

Keyword(s):

Deep Learning ◽

Drug Design ◽

De Novo ◽

Chemical Space ◽

3D Structure ◽

Space Distribution ◽

Generation Process ◽

Target Proteins ◽

Docking Simulations ◽

Molecular Generator

Recently, molecular generation models based on deep learning have attracted significant attention in drug discovery. However, most existing molecular generation models have a serious limitation in the context of drug design wherein they do not sufficiently consider the effect of the three-dimensional (3D) structure of the target protein in the generation process. In this study, we developed a new deep learning-based molecular generator, SBMolGen, that integrates a recurrent neural network, a Monte Carlo tree search, and docking simulations. The results of an evaluation using four target proteins (two kinases and two G protein-coupled receptors) showed that the generated molecules had a better binding affinity score (docking score) than the known active compounds, and they possessed a broader chemical space distribution. SBMolGen not only generates novel binding active molecules but also presents 3D docking poses with target proteins, which will be useful in subsequent drug design.

Download Full-text