scholarly journals A New Family of Similarity Measures for Scoring Confidence of Protein Interactions using Gene Ontology

2018 ◽  
Author(s):  
Madhusudan Paul ◽  
Ashish Anand
Keyword(s):  
Gene Ontology ◽  
Protein Interactions ◽  
Large Scale ◽  
Similarity Measures ◽  
Confidence Score ◽  
False Positives ◽  
Positive Interactions ◽  
Relative Depth ◽  
New Family ◽  
Edge Based

AbstractThe large-scale protein-protein interaction (PPI) data has the potential to play a significant role in the endeavor of understanding cellular processes. However, the presence of a considerable fraction of false positives is a bottleneck in realizing this potential. There have been continuous efforts to utilize complementary resources for scoring confidence of PPIs in a manner that false positive interactions get a low confidence score. Gene Ontology (GO), a taxonomy of biological terms to represent the properties of gene products and their relations, has been widely used for this purpose. We utilize GO to introduce a new set of specificity measures: Relative Depth Specificity (RDS), Relative Node-based Specificity (RNS), and Relative Edge-based Specificity (RES), leading to a new family of similarity measures. We use these similarity measures to obtain a confidence score for each PPI. We evaluate the new measures using four different benchmarks. We show that all the three measures are quite effective. Notably, RNS and RES more effectively distinguish true PPIs from false positives than the existing alternatives. RES also shows a robust set-discriminating power and can be useful for protein functional clustering as well.

scholarly journals DeepciRGO: functional prediction of circular RNAs through hierarchical deep neural networks using heterogeneous network features

2020 ◽  
Author(s):  
Lei Deng ◽  
Wei Lin ◽  
Jiacheng Wang ◽  
Jingpu Zhang
Keyword(s):  
Gene Ontology ◽  
Protein Interactions ◽  
Heterogeneous Network ◽  
Mammalian Cells ◽  
Noncoding Rna ◽  
Large Scale ◽  
Hierarchical Classification ◽  
Representation Learning ◽  
Classification Model ◽  
Circular Rnas

Abstract Circular RNAs (circRNAs) are special noncoding RNA molecules with closed loop structures. Compared with the traditional linear RNA, circRNA is more stable and not easily degraded. Many studies have shown that circRNAs are involved in the regulation of various diseases and cancers. Determining the functions of circRNAs in mammalian cells is of great significance for revealing their mechanism of action in physiological and pathological processes, diagnosis and treatment of diseases. However, determining the functions of circRNAs on a large scale is a challenging task because of the high experimental costs. In this paper, we present a hierarchical deep learning model, DeepciRGO, which can effectively predict gene ontology functions of circRNAs. We build a heterogeneous network containing circRNA co-expressions, protein-protein interactions (PPIs) and protein-circRNA interactions. The topology features of proteins and circRNAs are calculated using a novel representation learning approach Hin2vec across the heterogeneous network. Then, a deep multi-label hierarchical classification model is trained with the topology features to predict the biological process (BP) function in the Gene Ontology (GO) for each circRNA. In particular, we manually curated a benchmark dataset containing 185 GO annotations for 62 circRNAs, namely, circRNA2GO-62. The DeepciRGO achieves promising performance on the circRNA2GO-62 dataset with a maximum F-measure of 0.412, a recall score of 0.4, and an accuracy of 0.4, which are significantly better than other state-of-the-art RNA function prediction methods. In addition, we demonstrate the considerable potential of integrating multiple interactions and association networks.

scholarly journals Use of Chou’s 5-steps rule to predict the subcellular localization of gram-negative and gram-positive bacterial proteins by multi-label learning based on gene ontology annotation and profile alignment

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Hafida Bouziane ◽  
Abdallah Chouarfia
Keyword(s):  
Gene Ontology ◽  
Subcellular Localization ◽  
Protein Interactions ◽  
Protein Function ◽  
Large Scale ◽  
Biological Databases ◽  
Gram Positive ◽  
Essential Information ◽  
Gram Negative ◽  
Bacterial Proteins

AbstractTo date, many proteins generated by large-scale genome sequencing projects are still uncharacterized and subject to intensive investigations by both experimental and computational means. Knowledge of protein subcellular localization (SCL) is of key importance for protein function elucidation. However, it remains a challenging task, especially for multiple sites proteins known to shuttle between cell compartments to perform their proper biological functions and proteins which do not have significant homology to proteins of known subcellular locations. Due to their low-cost and reasonable accuracy, machine learning-based methods have gained much attention in this context with the availability of a plethora of biological databases and annotated proteins for analysis and benchmarking. Various predictive models have been proposed to tackle the SCL problem, using different protein sequence features pertaining to the subcellular localization, however, the overwhelming majority of them focuses on single localization and cover very limited cellular locations. The prediction was basically established on sorting signals, amino acids compositions, and homology. To improve the prediction quality, focus is actually on knowledge information extracted from annotation databases, such as protein–protein interactions and Gene Ontology (GO) functional domains annotation which has been recently a widely adopted and essential information for learning systems. To deal with such problem, in the present study, we considered SCL prediction task as a multi-label learning problem and tried to label both single site and multiple sites unannotated bacterial protein sequences by mining proteins homology relationships using both GO terms of protein homologs and PSI-BLAST profiles. The experiments using 5-fold cross-validation tests on the benchmark datasets showed a significant improvement on the results obtained by the proposed consensus multi-label prediction model which discriminates six compartments for Gram-negative and five compartments for Gram-positive bacterial proteins.

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

A Target-Based Method for Designing Heterochiral Cyclic Peptide Binders: De Novo Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
Cyclic Peptide ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

Target-Templated de novo Design of Macrocyclic D-/L-Peptides: Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Protein Protein Interactions ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>

scholarly journals Content-Based Estimation of Brain MRI Tilt in Three Orthogonal Directions

2021 ◽  
Author(s):  
Pooja Prabhu ◽  
A. K. Karunakar ◽  
Sanjib Sinha ◽  
N. Mariyappa ◽  
G. K. Bhargava ◽  
...  
Keyword(s):  
Large Scale ◽  
Brain Mri ◽  
Similarity Measures ◽  
Principal Component ◽  
Brain Anatomy ◽  
Morphological Operations ◽  
Mr Images ◽  
Tilt Correction ◽  
Brain Mr Images ◽  
The Brain

AbstractIn a general scenario, the brain images acquired from magnetic resonance imaging (MRI) may experience tilt, distorting brain MR images. The tilt experienced by the brain MR images may result in misalignment during image registration for medical applications. Manually correcting (or estimating) the tilt on a large scale is time-consuming, expensive, and needs brain anatomy expertise. Thus, there is a need for an automatic way of performing tilt correction in three orthogonal directions (X, Y, Z). The proposed work aims to correct the tilt automatically by measuring the pitch angle, yaw angle, and roll angle in X-axis, Z-axis, and Y-axis, respectively. For correction of the tilt around the Z-axis (pointing to the superior direction), image processing techniques, principal component analysis, and similarity measures are used. Also, for correction of the tilt around the X-axis (pointing to the right direction), morphological operations, and tilt correction around the Y-axis (pointing to the anterior direction), orthogonal regression is used. The proposed approach was applied to adjust the tilt observed in the T1- and T2-weighted MR images. The simulation study with the proposed algorithm yielded an error of 0.40 ± 0.09°, and it outperformed the other existing studies. The tilt angle (in degrees) obtained is ranged from 6.2 ± 3.94, 2.35 ± 2.61, and 5 ± 4.36 in X-, Z-, and Y-directions, respectively, by using the proposed algorithm. The proposed work corrects the tilt more accurately and robustly when compared with existing studies.

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