scholarly journals Systematic Modeling, Prediction, and Comparison of Domain–Peptide Affinities: Does it Work Effectively With the Peptide QSAR Methodology?

2022 ◽  
Vol 12 ◽  
Author(s):  
Qian Liu ◽  
Jing Lin ◽  
Li Wen ◽  
Shaozhou Wang ◽  
Peng Zhou ◽  
...  
Keyword(s):  
Large Scale ◽  
Quantitative Structure Activity Relationship ◽  
Linear Motif ◽  
Activity Data ◽  
Data Set ◽  
Binding Behavior ◽  
Protein Receptors ◽  
Direct Binding ◽  
Amino Acid Descriptors ◽  
Domain Peptide

The protein–protein association in cellular signaling networks (CSNs) often acts as weak, transient, and reversible domain–peptide interaction (DPI), in which a flexible peptide segment on the surface of one protein is recognized and bound by a rigid peptide-recognition domain from another. Reliable modeling and accurate prediction of DPI binding affinities would help to ascertain the diverse biological events involved in CSNs and benefit our understanding of various biological implications underlying DPIs. Traditionally, peptide quantitative structure-activity relationship (pQSAR) has been widely used to model and predict the biological activity of oligopeptides, which employs amino acid descriptors (AADs) to characterize peptide structures at sequence level and then statistically correlate the resulting descriptor vector with observed activity data via regression. However, the QSAR has not yet been widely applied to treat the direct binding behavior of large-scale peptide ligands to their protein receptors. In this work, we attempted to clarify whether the pQSAR methodology can work effectively for modeling and predicting DPI affinities in a high-throughput manner? Over twenty thousand short linear motif (SLiM)-containing peptide segments involved in SH3, PDZ and 14-3-3 domain-medicated CSNs were compiled to define a comprehensive sequence-based data set of DPI affinities, which were represented by the Boehringer light units (BLUs) derived from previous arbitrary light intensity assays following SPOT peptide synthesis. Four sophisticated MLMs (MLMs) were then utilized to perform pQSAR modeling on the set described with different AADs to systematically create a variety of linear and nonlinear predictors, and then verified by rigorous statistical test. It is revealed that the genome-wide DPI events can only be modeled qualitatively or semiquantitatively with traditional pQSAR strategy due to the intrinsic disorder of peptide conformation and the potential interplay between different peptide residues. In addition, the arbitrary BLUs used to characterize DPI affinity values were measured via an indirect approach, which may not very reliable and may involve strong noise, thus leading to a considerable bias in the modeling. The Rprd2 = 0.7 can be considered as the upper limit of external generalization ability of the pQSAR methodology working on large-scale DPI affinity data.

scholarly journals Deep Imputation on Large-Scale Drug Discovery Data

2021 ◽  
Author(s):  
Benedict Irwin ◽  
Thomas Whitehead ◽  
Scott Rowland ◽  
Samar Mahmoud ◽  
Gareth Conduit ◽  
...  
Keyword(s):  
Deep Learning ◽  
Drug Discovery ◽  
High Throughput Screening ◽  
Large Scale ◽  
Early Stage ◽  
Quantitative Structure Activity Relationship ◽  
Biological Properties ◽  
Data Repository ◽  
Activity Data ◽  
Predicted Values

More accurate predictions of the biological properties of chemical compounds would guide the selection and design of new compounds in drug discovery and help to address the enormous cost and low success-rate of pharmaceutical R&D. However this domain presents a significant challenge for AI methods due to the sparsity of compound data and the noise inherent in results from biological experiments. In this paper, we demonstrate how data imputation using deep learning provides substantial improvements over quantitative structure-activity relationship (QSAR) machine learning models that are widely applied in drug discovery. We present the largest-to-date successful application of deep-learning imputation to datasets which are comparable in size to the corporate data repository of a pharmaceutical company (678,994 compounds by 1166 endpoints). We demonstrate this improvement for three areas of practical application linked to distinct use cases; i) target activity data compiled from a range of drug discovery projects, ii) a high value and heterogeneous dataset covering complex absorption, distribution, metabolism and elimination properties and, iii) high throughput screening data, testing the algorithm’s limits on early-stage noisy and very sparse data. Achieving median coefficients of determination, R, of 0.69, 0.36 and 0.43 respectively across these applications, the deep learning imputation method offers an unambiguous improvement over random forest QSAR methods, which achieve median R values of 0.28, 0.19 and 0.23 respectively. We also demonstrate that robust estimates of the uncertainties in the predicted values correlate strongly with the accuracies in prediction, enabling greater confidence in decision-making based on the imputed values.

scholarly journals Collecting public RGB-D datasets for human daily activity recognition

2017 ◽  
Vol 14 (4) ◽  
pp. 172988141770907 ◽  
Author(s):  
Hanbo Wu ◽  
Xin Ma ◽  
Zhimeng Zhang ◽  
Haibo Wang ◽  
Yibin Li
Keyword(s):  
Activity Recognition ◽  
Daily Activity ◽  
Visual Cues ◽  
Large Scale ◽  
Hot Spot ◽  
Feature Representation ◽  
Data Sets ◽  
Activity Data ◽  
Data Set ◽  
Depth Motion Maps

Human daily activity recognition has been a hot spot in the field of computer vision for many decades. Despite best efforts, activity recognition in naturally uncontrolled settings remains a challenging problem. Recently, by being able to perceive depth and visual cues simultaneously, RGB-D cameras greatly boost the performance of activity recognition. However, due to some practical difficulties, the publicly available RGB-D data sets are not sufficiently large for benchmarking when considering the diversity of their activities, subjects, and background. This severely affects the applicability of complicated learning-based recognition approaches. To address the issue, this article provides a large-scale RGB-D activity data set by merging five public RGB-D data sets that differ from each other on many aspects such as length of actions, nationality of subjects, or camera angles. This data set comprises 4528 samples depicting 7 action categories (up to 46 subcategories) performed by 74 subjects. To verify the challengeness of the data set, three feature representation methods are evaluated, which are depth motion maps, spatiotemporal depth cuboid similarity feature, and curvature space scale. Results show that the merged large-scale data set is more realistic and challenging and therefore more suitable for benchmarking.

scholarly journals Translating Videos into Synthetic Training Data for Wearable Sensor-Based Activity Recognition Systems Using Residual Deep Convolutional Networks

2021 ◽  
Vol 11 (7) ◽  
pp. 3094
Author(s):  
Vitor Fortes Rey ◽  
Kamalveer Kaur Garewal ◽  
Paul Lukowicz
Keyword(s):  
Computer Vision ◽  
Regression Model ◽  
Activity Recognition ◽  
Language Processing ◽  
Large Scale ◽  
Simulated Data ◽  
Training Data ◽  
Sensor Data ◽  
Activity Data ◽  
Data Set

Human activity recognition (HAR) using wearable sensors has benefited much less from recent advances in Deep Learning than fields such as computer vision and natural language processing. This is, to a large extent, due to the lack of large scale (as compared to computer vision) repositories of labeled training data for sensor-based HAR tasks. Thus, for example, ImageNet has images for around 100,000 categories (based on WordNet) with on average 1000 images per category (therefore up to 100,000,000 samples). The Kinetics-700 video activity data set has 650,000 video clips covering 700 different human activities (in total over 1800 h). By contrast, the total length of all sensor-based HAR data sets in the popular UCI machine learning repository is less than 63 h, with around 38 of those consisting of simple mode of locomotion activities like walking, standing or cycling. In our research we aim to facilitate the use of online videos, which exist in ample quantities for most activities and are much easier to label than sensor data, to simulate labeled wearable motion sensor data. In previous work we already demonstrated some preliminary results in this direction, focusing on very simple, activity specific simulation models and a single sensor modality (acceleration norm). In this paper, we show how we can train a regression model on generic motions for both accelerometer and gyro signals and then apply it to videos of the target activities to generate synthetic Inertial Measurement Units (IMU) data (acceleration and gyro norms) that can be used to train and/or improve HAR models. We demonstrate that systems trained on simulated data generated by our regression model can come to within around 10% of the mean F1 score of a system trained on real sensor data. Furthermore, we show that by either including a small amount of real sensor data for model calibration or simply leveraging the fact that (in general) we can easily generate much more simulated data from video than we can collect its real version, the advantage of the latter can eventually be equalized.

scholarly journals The transcription factor Leu3 shows differential binding behavior in response to changing leucine availability

2020 ◽  
Vol 367 (13) ◽  
Author(s):  
Christoph S Börlin ◽  
Jens Nielsen ◽  
Verena Siewers
Keyword(s):  
Transcription Factor ◽  
Large Scale ◽  
Target Genes ◽  
Binding Activity ◽  
Leucine Supplementation ◽  
Yeast Saccharomyces Cerevisiae ◽  
Data Set ◽  
Binding Behavior ◽  
Binding Site Identification ◽  
Site Identification

ABSTRACT The main transcriptional regulator of leucine biosynthesis in the yeast Saccharomyces cerevisiae is the transcription factor Leu3. It has previously been reported that Leu3 always binds to its target genes, but requires activation to induce their expression. In a recent large-scale study of high-resolution transcription factor binding site identification, we showed that Leu3 has divergent binding sites in different cultivation conditions, thereby questioning the results of earlier studies. Here, we present a follow-up study using chromatin immunoprecipitation followed by sequencing (ChIP-seq) to investigate the influence of leucine supplementation on Leu3 binding activity and strength. With this new data set we are able to show that Leu3 exhibits changes in binding activity in response to changing levels of leucine availability.

scholarly journals Deep Imputation on Large-Scale Drug Discovery Data

2021 ◽  
Author(s):  
Benedict Irwin ◽  
Thomas Whitehead ◽  
Scott Rowland ◽  
Samar Mahmoud ◽  
Gareth Conduit ◽  
...  
Keyword(s):  
Deep Learning ◽  
Drug Discovery ◽  
High Throughput Screening ◽  
Large Scale ◽  
Early Stage ◽  
Quantitative Structure Activity Relationship ◽  
Biological Properties ◽  
Data Repository ◽  
Activity Data ◽  
Predicted Values

More accurate predictions of the biological properties of chemical compounds would guide the selection and design of new compounds in drug discovery and help to address the enormous cost and low success-rate of pharmaceutical R&D. However this domain presents a significant challenge for AI methods due to the sparsity of compound data and the noise inherent in results from biological experiments. In this paper, we demonstrate how data imputation using deep learning provides substantial improvements over quantitative structure-activity relationship (QSAR) machine learning models that are widely applied in drug discovery. We present the largest-to-date successful application of deep-learning imputation to datasets which are comparable in size to the corporate data repository of a pharmaceutical company (678,994 compounds by 1166 endpoints). We demonstrate this improvement for three areas of practical application linked to distinct use cases; i) target activity data compiled from a range of drug discovery projects, ii) a high value and heterogeneous dataset covering complex absorption, distribution, metabolism and elimination properties and, iii) high throughput screening data, testing the algorithm’s limits on early-stage noisy and very sparse data. Achieving median coefficients of determination, R, of 0.69, 0.36 and 0.43 respectively across these applications, the deep learning imputation method offers an unambiguous improvement over random forest QSAR methods, which achieve median R values of 0.28, 0.19 and 0.23 respectively. We also demonstrate that robust estimates of the uncertainties in the predicted values correlate strongly with the accuracies in prediction, enabling greater confidence in decision-making based on the imputed values.

ProGen:Provenance database generator for large-scale data set

2009 ◽  
Vol 28 (11) ◽  
pp. 2737-2740
Author(s):  
Xiao ZHANG ◽  
Shan WANG ◽  
Na LIAN
Keyword(s):  
Large Scale ◽  
Data Set ◽  
Large Scale Data ◽  
Scale Data

Interpretable SMILES-based QSAR model of inhibitory activity of sirtuins 1 and 2

2020 ◽  
Vol 23 ◽  
Author(s):  
Apilak Worachartcheewan ◽  
Alla P. Toropova ◽  
Andrey A. Toropov ◽  
Reny Pratiwi ◽  
Virapong Prachayasittikul ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Rational Design ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Sirtuin 1 ◽  
Data Set ◽  
Functional Roles ◽  
Molecular Features ◽  
Oecd Principles ◽  
Qsar Models

Background: Sirtuin 1 (Sirt1) and sirtuin 2 (Sirt2) are NAD+ -dependent histone deacetylases which play important functional roles in removal of the acetyl group of acetyl-lysine substrates. Considering the dysregulation of Sirt1 and Sirt2 as etiological causes of diseases, Sirt1 and Sirt2 are lucrative target proteins for treatment, thus there has been great interest in the development of Sirt1 and Sirt2 inhibitors. Objective: This study compiled the bioactivity data of Sirt1 and Sirt2 for the construction of quantitative structure-activity relationship (QSAR) models in accordance with the OECD principles. Method: Simplified molecular input line entry system (SMILES)-based molecular descriptors were used to characterize the molecular features of inhibitors while the Monte Carlo method of the CORAL software was employed for multivariate analysis. The data set was subjected to 3 random splits in which each split separated the data into 4 subsets consisting of training, invisible training, calibration and external sets. Results: Statistical indices for the evaluation of QSAR models suggested good statistical quality for models of Sirt1 and Sirt2 inhibitors. Furthermore, mechanistic interpretation of molecular substructures that are responsible for modulating the bioactivity (i.e. promoters of increase or decrease of bioactivity) was extracted via the analysis of correlation weights. It exhibited molecular features involved Sirt1 and Sirt2 inhibitors. Conclusion: It is anticipated that QSAR models presented herein can be useful as guidelines in the rational design of potential Sirt1 and Sirt2 inhibitors for the treatment of Sirtuin-related diseases.

Integrative Data Analysis from a Unifying Research Synthesis Perspective

2018 ◽  
Author(s):  
Eun-Young Mun ◽  
Anne E. Ray
Keyword(s):  
Data Analysis ◽  
Large Scale ◽  
Research Synthesis ◽  
Alcohol Intervention ◽  
Data Set ◽  
Integrative Data Analysis ◽  
Level Data ◽  
Model Complex ◽  
Wide Range ◽  
Individual Participant

Integrative data analysis (IDA) is a promising new approach in psychological research and has been well received in the field of alcohol research. This chapter provides a larger unifying research synthesis framework for IDA. Major advantages of IDA of individual participant-level data include better and more flexible ways to examine subgroups, model complex relationships, deal with methodological and clinical heterogeneity, and examine infrequently occurring behaviors. However, between-study heterogeneity in measures, designs, and samples and systematic study-level missing data are significant barriers to IDA and, more broadly, to large-scale research synthesis. Based on the authors’ experience working on the Project INTEGRATE data set, which combined individual participant-level data from 24 independent college brief alcohol intervention studies, it is also recognized that IDA investigations require a wide range of expertise and considerable resources and that some minimum standards for reporting IDA studies may be needed to improve transparency and quality of evidence.

Financial distress determinants among SMEs: empirical evidence from Sweden

2020 ◽  
Vol 47 (3) ◽  
pp. 547-560 ◽  
Author(s):  
Darush Yazdanfar ◽  
Peter Öhman
Keyword(s):  
Financial Crisis ◽  
Financial Distress ◽  
Large Scale ◽  
Global Financial Crisis ◽  
Binary Logistic Regression ◽  
Data Availability ◽  
Cross Sectional ◽  
Data Set ◽  
Content Type ◽  
The Global Financial Crisis

PurposeThe purpose of this study is to empirically investigate determinants of financial distress among small and medium-sized enterprises (SMEs) during the global financial crisis and post-crisis periods.Design/methodology/approachSeveral statistical methods, including multiple binary logistic regression, were used to analyse a longitudinal cross-sectional panel data set of 3,865 Swedish SMEs operating in five industries over the 2008–2015 period.FindingsThe results suggest that financial distress is influenced by macroeconomic conditions (i.e. the global financial crisis) and, in particular, by various firm-specific characteristics (i.e. performance, financial leverage and financial distress in previous year). However, firm size and industry affiliation have no significant relationship with financial distress.Research limitationsDue to data availability, this study is limited to a sample of Swedish SMEs in five industries covering eight years. Further research could examine the generalizability of these findings by investigating other firms operating in other industries and other countries.Originality/valueThis study is the first to examine determinants of financial distress among SMEs operating in Sweden using data from a large-scale longitudinal cross-sectional database.

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