scholarly journals SOLart: a structure-based method to predict protein solubility and aggregation

2019 ◽  
Author(s):  
Qingzhen Hou ◽  
Jean Marc Kwasigroch ◽  
Marianne Rooman ◽  
Fabrizio Pucci
Keyword(s):  
Solvent Accessibility ◽  
Pearson Correlation ◽  
Protein Solubility ◽  
Independent Set ◽  
Supplementary Information ◽  
Training Dataset ◽  
Solubility Prediction ◽  
High Concentration ◽  
Structural Genomic ◽  
Genomic Studies

Abstract Motivation The solubility of a protein is often decisive for its proper functioning. Lack of solubility is a major bottleneck in high-throughput structural genomic studies and in high-concentration protein production, and the formation of protein aggregates causes a wide variety of diseases. Since solubility measurements are time-consuming and expensive, there is a strong need for solubility prediction tools. Results We have recently introduced solubility-dependent distance potentials that are able to unravel the role of residue–residue interactions in promoting or decreasing protein solubility. Here, we extended their construction by defining solubility-dependent potentials based on backbone torsion angles and solvent accessibility, and integrated them, together with other structure- and sequence-based features, into a random forest model trained on a set of Escherichia coli proteins with experimental structures and solubility values. We thus obtained the SOLart protein solubility predictor, whose most informative features turned out to be folding free energy differences computed from our solubility-dependent statistical potentials. SOLart performances are very good, with a Pearson correlation coefficient between experimental and predicted solubility values of almost 0.7 both in cross-validation on the training dataset and in an independent set of Saccharomyces cerevisiae proteins. On test sets of modeled structures, only a limited drop in performance is observed. SOLart can thus be used with both high-resolution and low-resolution structures, and clearly outperforms state-of-art solubility predictors. It is available through a user-friendly webserver, which is easy to use by non-expert scientists. Availability and implementation The SOLart webserver is freely available at http://babylone.ulb.ac.be/SOLART/. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Solart: A Structure-Based Method To Predict Protein Solubility And Aggregation

2019 ◽  
Author(s):  
Q. Hou ◽  
J. M. Kwasigroch ◽  
M. Rooman ◽  
F. Pucci
Keyword(s):  
Solvent Accessibility ◽  
Pearson Correlation ◽  
Protein Solubility ◽  
Independent Set ◽  
Training Dataset ◽  
Solubility Prediction ◽  
High Concentration ◽  
Structural Genomic ◽  
Genomic Studies ◽  
User Friendly

ABSTRACTMotivationThe solubility of a protein is often decisive for its proper functioning. Lack of solubility is a major bottleneck in high-throughput structural genomic studies and in high-concentration protein production, and the formation of protein aggregates causes a wide variety of diseases. Since solubility measurements are time-consuming and expensive, there is a strong need for solubility prediction tools.ResultsWe have recently introduced solubility-dependent distance potentials that are able to unravel the role of residue-residue interactions in promoting or decreasing protein solubility. Here, we extended their construction by defining solubility-dependent potentials based on backbone torsion angles and solvent accessibility, and integrated them, together with other structure- and sequence-based features, into a random forest model trained on a set of E. coli proteins with experimental structures and solubility values. We thus obtained the SOLart protein solubility predictor, whose most informative features turned out to be folding free energy differences computed from our solubility-dependent statistical potentials. SOLart performances are very good, with a Pearson correlation coefficient between experimental and predicted solubility values of 0.7 both in the training dataset and on an independent set of S. Cerevisiae proteins. On test sets of modeled structures, only a limited drop in performance is observed. SOLart can thus be used with both high-resolution and low-resolution structures, and clearly outperforms state-of-art solubility predictors. It is available through a user-friendly webserver, which is easy to use by non-expert scientists.AvailabilityThe SOLart webserver is freely available at babylone.ulb.ac.be/SOLART/

scholarly journals Structure-aware Protein Solubility Prediction From Sequence Through Graph Convolutional Network And Predicted Contact Map

2020 ◽  
Author(s):  
Jianwen Chen ◽  
Shuangjia Zheng ◽  
Huiying Zhao ◽  
Yuedong Yang
Keyword(s):  
Structural Information ◽  
Protein Solubility ◽  
Supplementary Information ◽  
Solubility Prediction ◽  
Contact Map ◽  
Convolutional Network ◽  
Contact Maps ◽  
Protein Prediction ◽  
The One ◽  
The Cost

AbstractMotivationProtein solubility is significant in producing new soluble proteins that can reduce the cost of biocatalysts or therapeutic agents. Therefore, a computational model is highly desired to accurately predict protein solubility from the amino acid sequence. Many methods have been developed, but they are mostly based on the one-dimensional embedding of amino acids that is limited to catch spatially structural information.ResultsIn this study, we have developed a new structure-aware method to predict protein solubility by attentive graph convolutional network (GCN), where the protein topology attribute graph was constructed through predicted contact maps from the sequence. GraphSol was shown to substantially out-perform other sequence-based methods. The model was proven to be stable by consistent R2 of 0.48 in both the cross-validation and independent test of the eSOL dataset. To our best knowledge, this is the first study to utilize the GCN for sequence-based predictions. More importantly, this architecture could be extended to other protein prediction tasks.AvailabilityThe package is available at http://[email protected] informationSupplementary data are available at Bioinformatics online.

scholarly journals Solubility-Weighted Index: fast and accurate prediction of protein solubility

2020 ◽  
Vol 36 (18) ◽  
pp. 4691-4698 ◽  
Author(s):  
Bikash K Bhandari ◽  
Paul P Gardner ◽  
Chun Shen Lim
Keyword(s):  
Protein Expression ◽  
Protein Production ◽  
Protein Solubility ◽  
Region Of Interest ◽  
Supplementary Information ◽  
Structural Flexibility ◽  
Web Interface ◽  
Solubility Prediction ◽  
Prediction Tools ◽  
Weighted Index

Abstract Motivation Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified. Results We have discovered that global structural flexibility, which can be modeled by normalized B-factors, accurately predicts the solubility of 12 216 recombinant proteins expressed in Escherichia coli. We have optimized these B-factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the ‘Solubility-Weighted Index’ (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed ‘SoDoPE’ (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximizing both protein expression and solubility. Availability and implementation The SoDoPE web server and source code are freely available at https://tisigner.com/sodope and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS, respectively. The code and data for reproducing our analysis can be found at https://github.com/Gardner-BinfLab/SoDoPE_paper_2020. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Single-sequence and profile-based prediction of RNA solvent accessibility using dilated convolutional neural network

2020 ◽  
Author(s):  
Anil Kumar Hanumanthappa ◽  
Jaswinder Singh ◽  
Kuldip Paliwal ◽  
Jaspreet Singh ◽  
Yaoqi Zhou
Keyword(s):  
Neural Network ◽  
Convolutional Neural Network ◽  
Solvent Accessibility ◽  
Pearson Correlation ◽  
Functional Characterization ◽  
Homology Search ◽  
Supplementary Information ◽  
Functional Regions ◽  
Comparable Performance ◽  
Single Sequence

Abstract Motivation RNA solvent accessibility, similar to protein solvent accessibility, reflects the structural regions that are accessible to solvents or other functional biomolecules, and plays an important role for structural and functional characterization. Unlike protein solvent accessibility, only a few tools are available for predicting RNA solvent accessibility despite the fact that millions of RNA transcripts have unknown structures and functions. Also, these tools have limited accuracy. Here, we have developed RNAsnap2 that uses a dilated convolutional neural network with a new feature, based on predicted base-pairing probabilities from LinearPartition. Results Using the same training set from the recent predictor RNAsol, RNAsnap2 provides an 11% improvement in median Pearson Correlation Coefficient (PCC) and 9% improvement in mean absolute errors for the same test set of 45 RNA chains. A larger improvement (22% in median PCC) is observed for 31 newly deposited RNA chains that are non-redundant and independent from the training and the test sets. A single-sequence version of RNAsnap2 (i.e. without using sequence profiles generated from homology search by Infernal) has achieved comparable performance to the profile-based RNAsol. In addition, RNAsnap2 has achieved comparable performance for protein-bound and protein-free RNAs. Both RNAsnap2 and RNAsnap2 (SingleSeq) are expected to be useful for searching structural signatures and locating functional regions of non-coding RNAs. Availability and implementation Standalone-versions of RNAsnap2 and RNAsnap2 (SingleSeq) are available at https://github.com/jaswindersingh2/RNAsnap2. Direct prediction can also be made at https://sparks-lab.org/server/rnasnap2. The datasets used in this research can also be downloaded from the GITHUB and the webserver mentioned above. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Transformers-sklearn: a toolkit for medical language understanding with transformer-based models

2021 ◽  
Vol 21 (S2) ◽  
Author(s):  
Feihong Yang ◽  
Xuwen Wang ◽  
Hetong Ma ◽  
Jiao Li
Keyword(s):  
Language Processing ◽  
Pearson Correlation ◽  
Fine Tuning ◽  
Entity Recognition ◽  
Training Dataset ◽  
Training Methods ◽  
Code Size ◽  
Model Framework ◽  
Language Understanding ◽  
Medical Language

Abstract Background Transformer is an attention-based architecture proven the state-of-the-art model in natural language processing (NLP). To reduce the difficulty of beginning to use transformer-based models in medical language understanding and expand the capability of the scikit-learn toolkit in deep learning, we proposed an easy to learn Python toolkit named transformers-sklearn. By wrapping the interfaces of transformers in only three functions (i.e., fit, score, and predict), transformers-sklearn combines the advantages of the transformers and scikit-learn toolkits. Methods In transformers-sklearn, three Python classes were implemented, namely, BERTologyClassifier for the classification task, BERTologyNERClassifier for the named entity recognition (NER) task, and BERTologyRegressor for the regression task. Each class contains three methods, i.e., fit for fine-tuning transformer-based models with the training dataset, score for evaluating the performance of the fine-tuned model, and predict for predicting the labels of the test dataset. transformers-sklearn is a user-friendly toolkit that (1) Is customizable via a few parameters (e.g., model_name_or_path and model_type), (2) Supports multilingual NLP tasks, and (3) Requires less coding. The input data format is automatically generated by transformers-sklearn with the annotated corpus. Newcomers only need to prepare the dataset. The model framework and training methods are predefined in transformers-sklearn. Results We collected four open-source medical language datasets, including TrialClassification for Chinese medical trial text multi label classification, BC5CDR for English biomedical text name entity recognition, DiabetesNER for Chinese diabetes entity recognition and BIOSSES for English biomedical sentence similarity estimation. In the four medical NLP tasks, the average code size of our script is 45 lines/task, which is one-sixth the size of transformers’ script. The experimental results show that transformers-sklearn based on pretrained BERT models achieved macro F1 scores of 0.8225, 0.8703 and 0.6908, respectively, on the TrialClassification, BC5CDR and DiabetesNER tasks and a Pearson correlation of 0.8260 on the BIOSSES task, which is consistent with the results of transformers. Conclusions The proposed toolkit could help newcomers address medical language understanding tasks using the scikit-learn coding style easily. The code and tutorials of transformers-sklearn are available at https://doi.org/10.5281/zenodo.4453803. In future, more medical language understanding tasks will be supported to improve the applications of transformers_sklearn.

scholarly journals Accurate estimation of isoelectric point of protein and peptide based on amino acid sequences

2015 ◽  
Vol 32 (6) ◽  
pp. 821-827 ◽  
Author(s):  
Enrique Audain ◽  
Yassel Ramos ◽  
Henning Hermjakob ◽  
Darren R. Flower ◽  
Yasset Perez-Riverol
Keyword(s):  
Machine Learning ◽  
Isoelectric Point ◽  
Learning Algorithms ◽  
Machine Learning Algorithms ◽  
Basis Set ◽  
Superior Performance ◽  
Supplementary Information ◽  
Training Dataset ◽  
Accurate Estimation ◽  
Prediction Methods

Abstract Motivation: In any macromolecular polyprotic system—for example protein, DNA or RNA—the isoelectric point—commonly referred to as the pI—can be defined as the point of singularity in a titration curve, corresponding to the solution pH value at which the net overall surface charge—and thus the electrophoretic mobility—of the ampholyte sums to zero. Different modern analytical biochemistry and proteomics methods depend on the isoelectric point as a principal feature for protein and peptide characterization. Protein separation by isoelectric point is a critical part of 2-D gel electrophoresis, a key precursor of proteomics, where discrete spots can be digested in-gel, and proteins subsequently identified by analytical mass spectrometry. Peptide fractionation according to their pI is also widely used in current proteomics sample preparation procedures previous to the LC-MS/MS analysis. Therefore accurate theoretical prediction of pI would expedite such analysis. While such pI calculation is widely used, it remains largely untested, motivating our efforts to benchmark pI prediction methods. Results: Using data from the database PIP-DB and one publically available dataset as our reference gold standard, we have undertaken the benchmarking of pI calculation methods. We find that methods vary in their accuracy and are highly sensitive to the choice of basis set. The machine-learning algorithms, especially the SVM-based algorithm, showed a superior performance when studying peptide mixtures. In general, learning-based pI prediction methods (such as Cofactor, SVM and Branca) require a large training dataset and their resulting performance will strongly depend of the quality of that data. In contrast with Iterative methods, machine-learning algorithms have the advantage of being able to add new features to improve the accuracy of prediction. Contact: [email protected] Availability and Implementation: The software and data are freely available at https://github.com/ypriverol/pIR. Supplementary information: Supplementary data are available at Bioinformatics online.

scholarly journals Scoring functions for drug-effect similarity

2020 ◽  
Author(s):  
Stephan Struckmann ◽  
Mathias Ernst ◽  
Sarah Fischer ◽  
Nancy Mah ◽  
Georg Fuellen ◽  
...  
Keyword(s):  
Cell Line ◽  
Drug Effect ◽  
Pearson Correlation ◽  
Source Code ◽  
New Drugs ◽  
Supplementary Information ◽  
Disease Genes ◽  
Scoring Functions ◽  
Profile Changes

Abstract Motivation The difficulty to find new drugs and bring them to the market has led to an increased interest to find new applications for known compounds. Biological samples from many disease contexts have been extensively profiled by transcriptomics, and, intuitively, this motivates to search for compounds with a reversing effect on the expression of characteristic disease genes. However, disease effects may be cell line-specific and also depend on other factors, such as genetics and environment. Transcription profile changes between healthy and diseased cells relate in complex ways to profile changes gathered from cell lines upon stimulation with a drug. Despite these differences, we expect that there will be some similarity in the gene regulatory networks at play in both situations. The challenge is to match transcriptomes for both diseases and drugs alike, even though the exact molecular pathology/pharmacogenomics may not be known. Results We substitute the challenge to match a drug effect to a disease effect with the challenge to match a drug effect to the effect of the same drug at another concentration or in another cell line. This is welldefined, reproducible in vitro and in silico and extendable with external data. Based on the Connectivity Map (CMap) dataset, we combined 26 different similarity scores with six different heuristics to reduce the number of genes in the model. Such gene filters may also utilize external knowledge e.g. from biological networks. We found that no similarity score always outperforms all others for all drugs, but the Pearson correlation finds the same drug with the highest reliability. Results are improved by filtering for highly expressed genes and to a lesser degree for genes with large fold changes. Also a network-based reduction of contributing transcripts was beneficial, here implemented by the FocusHeuristics. We found no drop in prediction accuracy when reducing the whole transcriptome to the set of 1000 landmark genes of the CMap’s successor project Library of Integrated Network-based Cellular Signatures. All source code to re-analyze and extend the CMap data, the source code of heuristics, filters and their evaluation are available to propel the development of new methods for drug repurposing. Availability https://bitbucket.org/ibima/moldrugeffectsdb Contact [email protected] Supplementary information Supplementary data are available at Briefings in Bioinformatics online.

scholarly journals SphereCon—a method for precise estimation of residue relative solvent accessible area from limited structural information

2020 ◽  
Vol 36 (11) ◽  
pp. 3372-3378
Author(s):  
Alexander Gress ◽  
Olga V Kalinina
Keyword(s):  
Protein Function ◽  
Structural Information ◽  
Solvent Accessibility ◽  
Three Dimensional ◽  
Structural Data ◽  
Supplementary Information ◽  
Dimensional Structure ◽  
Relative Solvent Accessibility ◽  
Precise Measure ◽  
The Impact

Abstract Motivation In proteins, solvent accessibility of individual residues is a factor contributing to their importance for protein function and stability. Hence one might wish to calculate solvent accessibility in order to predict the impact of mutations, their pathogenicity and for other biomedical applications. A direct computation of solvent accessibility is only possible if all atoms of a protein three-dimensional structure are reliably resolved. Results We present SphereCon, a new precise measure that can estimate residue relative solvent accessibility (RSA) from limited data. The measure is based on calculating the volume of intersection of a sphere with a cone cut out in the direction opposite of the residue with surrounding atoms. We propose a method for estimating the position and volume of residue atoms in cases when they are not known from the structure, or when the structural data are unreliable or missing. We show that in cases of reliable input structures, SphereCon correlates almost perfectly with the directly computed RSA, and outperforms other previously suggested indirect methods. Moreover, SphereCon is the only measure that yields accurate results when the identities of amino acids are unknown. A significant novel feature of SphereCon is that it can estimate RSA from inter-residue distance and contact matrices, without any information about the actual atom coordinates. Availability and implementation https://github.com/kalininalab/spherecon. Contact [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Prediction of crude protein digestibility of animal by-product meals for dogs by the protein solubility in pepsin method

2014 ◽  
Vol 3 ◽  
Author(s):  
Iris M. Kawauchi ◽  
Nilva K. Sakomura ◽  
Cristiana F. F. Pontieri ◽  
Aline Rebelato ◽  
Thaila C. Putarov ◽  
...  
Keyword(s):  
Crude Protein ◽  
Pearson Correlation ◽  
Protein Solubility ◽  
Correlation Coefficients ◽  
Basal Diet ◽  
Protein Digestibility ◽  
Large Variability ◽  
The Relationship

AbstractAnimal by-product meals have large variability in crude protein (CP) content and digestibility. In vivo digestibility procedures are precise but laborious, and in vitro methods could be an alternative to evaluate and classify these ingredients. The present study reports prediction equations to estimate the CP digestibility of meat and bone meal (MBM) and poultry by-product meal (PM) using the protein solubility in pepsin method (PSP). Total tract CP digestibility of eight MBM and eight PM samples was determined in dogs by the substitution method. A basal diet was formulated for dog maintenance, and sixteen diets were produced by mixing 70 % of the basal diet and 30 % of each tested meal. Six dogs per diet were used to determine ingredient digestibility. In addition, PSP of the MBM and PM samples was determined using three pepsin concentrations: 0·02, 0·002 and 0·0002 %. The CP content of MBM and PM ranged from 39 to 46 % and 57 to 69 %, respectively, and their mean CP digestibility by dogs was 76 (2·4) and 85 (2·6) %, respectively. The pepsin concentration with higher Pearson correlation coefficients with the in vivo results were 0·0002 % for MBM (r 0·380; P = 0·008) and 0·02 % for PM (r 0·482; P = 0·005). The relationship between the in vivo and in vitro results was better explained by the following equations: CP digestibility of MBM = 61·7 + 0·2644 × PSP at 0·0002 % (P = 0·008; R2 0·126); and CP digestibility of PM = 54·1 + 0·3833 × PSP at 0·02 % (P = 0·005; R2 0·216). Although significant, the coefficients of determination were low, indicating that the models were weak and need to be used with caution.

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