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Abstract Background This research aims to increase our knowledge of amyloidoses. These disorders cause incorrect protein folding, affecting protein functionality (on structure). Fibrillar deposits are the basis of some wellknown diseases, such as Alzheimer, Creutzfeldt–Jakob diseases and type II diabetes. For many of these amyloid proteins, the relative precursors are known. Discovering new protein precursors involved in forming amyloid fibril deposits would improve understanding the pathological processes of amyloidoses. Results A new classifier, called ENTAIL, was developed using over than 4000 molecular descriptors. ENTAIL was based on the Naive Bayes Classifier with Unbounded Support and Gaussian Kernel Type, with an accuracy on the test set of 81.80%, SN of 100%, SP of 63.63% and an MCC of 0.683 on a balanced dataset. Conclusions The analysis carried out has demonstrated how, despite the various configurations of the tests, performances are superior in terms of performance on a balanced dataset.

Abstract Background Adaptor proteins play a key role in intercellular signal transduction, and dysfunctional adaptor proteins result in diseases. Understanding its structure is the first step to tackling the associated conditions, spurring ongoing interest in research into adaptor proteins with bioinformatics and computational biology. Our study aims to introduce a small, new, and superior model for protein classification, pushing the boundaries with new machine learning algorithms. Results We propose a novel transformer based model which includes convolutional block and fully connected layer. We input protein sequences from a database, extract PSSM features, then process it via our deep learning model. The proposed model is efficient and highly compact, achieving state-of-the-art performance in terms of area under the receiver operating characteristic curve, Matthew’s Correlation Coefficient and Receiver Operating Characteristics curve. Despite merely 20 hidden nodes translating to approximately 1% of the complexity of previous best known methods, the proposed model is still superior in results and computational efficiency. Conclusions The proposed model is the first transformer model used for recognizing adaptor protein, and outperforms all existing methods, having PSSM profiles as inputs that comprises convolutional blocks, transformer and fully connected layers for the use of classifying adaptor proteins.

Abstract Background SNARE proteins play an important role in different biological functions. This study aims to investigate the contribution of a new class of molecular descriptors (called SNARER) related to the chemical-physical properties of proteins in order to evaluate the performance of binary classifiers for SNARE proteins. Results We constructed a SNARE proteins balanced dataset, D128, and an unbalanced one, DUNI, on which we tested and compared the performance of the new descriptors presented here in combination with the feature sets (GAAC, CTDT, CKSAAP and 188D) already present in the literature. The machine learning algorithms used were Random Forest, k-Nearest Neighbors and AdaBoost and oversampling and subsampling techniques were applied to the unbalanced dataset. The addition of the SNARER descriptors increases the precision for all considered ML algorithms. In particular, on the unbalanced DUNI dataset the accuracy increases in parallel with the increase in sensitivity while on the balanced dataset D128 the accuracy increases compared to the counterpart without the addition of SNARER descriptors, with a strong improvement in specificity. Our best result is the combination of our descriptors SNARER with CKSAAP feature on the dataset D128 with 92.3% of accuracy, 90.1% for sensitivity and 95% for specificity with the RF algorithm. Conclusions The performed analysis has shown how the introduction of molecular descriptors linked to the chemical-physical and structural characteristics of the proteins can improve the classification performance. Additionally, it was pointed out that performance can change based on using a balanced or unbalanced dataset. The balanced nature of training can significantly improve forecast accuracy.

Background: This research aims to increase our knowledge of amyloidoses. These disorders cause incorrect protein folding, affecting protein functionality (on structure). Fibrillar deposits are the basis of some wellknown diseases, such as Alzheimer, Creutzfeldt–Jakob diseases and type II diabetes. For many of these amyloid proteins, the relative precursors are known. Discovering new protein precursors involved in forming amyloid fibril deposits would improve understanding the pathological processes of amyloidoses. Results: A new classifier, called ENTAIL, was developed using over than 4000 molecular descriptors. ENTAIL was based on the Naive Bayes Classifier with Unbounded Support and Gaussian Kernel Type, with an accuracy on the test set of 81.80%, SN of 100%, SP of 63.63% and an MCC of 0.683 on a balanced dataset. Conclusions: The analysis carried out has demonstrated how, despite the various configurations of the tests, performances are superior in terms of performance on a balanced dataset. [ABSTRACT FROM AUTHOR]

Background: Adaptor proteins play a key role in intercellular signal transduction, and dysfunctional adaptor proteins result in diseases. Understanding its structure is the first step to tackling the associated conditions, spurring ongoing interest in research into adaptor proteins with bioinformatics and computational biology. Our study aims to introduce a small, new, and superior model for protein classification, pushing the boundaries with new machine learning algorithms. Results: We propose a novel transformer based model which includes convolutional block and fully connected layer. We input protein sequences from a database, extract PSSM features, then process it via our deep learning model. The proposed model is efficient and highly compact, achieving state-of-the-art performance in terms of area under the receiver operating characteristic curve, Matthew's Correlation Coefficient and Receiver Operating Characteristics curve. Despite merely 20 hidden nodes translating to approximately 1% of the complexity of previous best known methods, the proposed model is still superior in results and computational efficiency. Conclusions: The proposed model is the first transformer model used for recognizing adaptor protein, and outperforms all existing methods, having PSSM profiles as inputs that comprises convolutional blocks, transformer and fully connected layers for the use of classifying adaptor proteins. [ABSTRACT FROM AUTHOR]

Background: SNARE proteins play an important role in different biological functions. This study aims to investigate the contribution of a new class of molecular descriptors (called SNARER) related to the chemical-physical properties of proteins in order to evaluate the performance of binary classifiers for SNARE proteins. Results: We constructed a SNARE proteins balanced dataset, D128, and an unbalanced one, DUNI, on which we tested and compared the performance of the new descriptors presented here in combination with the feature sets (GAAC, CTDT, CKSAAP and 188D) already present in the literature. The machine learning algorithms used were Random Forest, k-Nearest Neighbors and AdaBoost and oversampling and subsampling techniques were applied to the unbalanced dataset. The addition of the SNARER descriptors increases the precision for all considered ML algorithms. In particular, on the unbalanced DUNI dataset the accuracy increases in parallel with the increase in sensitivity while on the balanced dataset D128 the accuracy increases compared to the counterpart without the addition of SNARER descriptors, with a strong improvement in specificity. Our best result is the combination of our descriptors SNARER with CKSAAP feature on the dataset D128 with 92.3% of accuracy, 90.1% for sensitivity and 95% for specificity with the RF algorithm. Conclusions: The performed analysis has shown how the introduction of molecular descriptors linked to the chemical-physical and structural characteristics of the proteins can improve the classification performance. Additionally, it was pointed out that performance can change based on using a balanced or unbalanced dataset. The balanced nature of training can significantly improve forecast accuracy. [ABSTRACT FROM AUTHOR]

Background: Azopirillum brasilense is a plant-growth promoting nitrogen-fixing bacteria that is used as bio-fertilizer in agriculture. Since nitrogen fixation has a high-energy demand, the reduction of N2 to NH4+ by nitrogenase occurs only under limiting conditions of NH4+ and O2. Moreover, the synthesis and activity of nitrogenase is highly regulated to prevent energy waste. In A. brasilense nitrogenase activity is regulated by the products of draG and draT. The product of the draB gene, located downstream in the draTGB operon, may be involved in the regulation of nitrogenase activity by an, as yet, unknown mechanism. Results: A deep in silico analysis of the product of draB was undertaken aiming at suggesting its possible function and involvement with DraT and DraG in the regulation of nitrogenase activity in A. brasilense. In this work, we present a new artificial intelligence strategy for protein classification, named ProClaT. The features used by the pattern recognition model were derived from the primary structure of the DraB homologous proteins, calculated by a ProClaT internal algorithm. ProClaT was applied to this case study and the results revealed that the A. brasilense draB gene codes for a protein highly similar to the nitrogenase associated NifO protein of Azotobacter vinelandii. Conclusions: This tool allowed the reclassification of DraB/NifO homologous proteins, hypothetical, conserved hypothetical and those annotated as putative arsenate reductase, ArsC, as NifO-like. An analysis of co-occurrence of draB, draT, draG and of other nif genes was performed, suggesting the involvement of draB (nifO) in nitrogen fixation, however, without the definition of a specific function. [ABSTRACT FROM AUTHOR]

Background: The function of a protein can be deciphered with higher accuracy from its structure than from its amino acid sequence. Due to the huge gap in the available protein sequence and structural space, tools that can generate functionally homogeneous clusters using only the sequence information, hold great importance. For this, traditional alignment-based tools work well in most cases and clustering is performed on the basis of sequence similarity. But, in the case of multi-domain proteins, the alignment quality might be poor due to varied lengths of the proteins, domain shuffling or circular permutations. Multi-domain proteins are ubiquitous in nature, hence alignment-free tools, which overcome the shortcomings of alignment-based protein comparison methods, are required. Further, existing tools classify proteins using only domain-level information and hence miss out on the information encoded in the tethered regions or accessory domains. Our method, on the other hand, takes into account the full-length sequence of a protein, consolidating the complete sequence information to understand a given protein better. Results: Our web-server, CLAP (Classification of Proteins), is one such alignment-free software for automatic classification of protein sequences. It utilizes a pattern-matching algorithm that assigns local matching scores (LMS) to residues that are a part of the matched patterns between two sequences being compared. CLAP works on full-length sequences and does not require prior domain definitions. Pilot studies undertaken previously on protein kinases and immunoglobulins have shown that CLAP yields clusters, which have high functional and domain architectural similarity. Moreover, parsing at a statistically determined cut-off resulted in clusters that corroborated with the sub-family level classification of that particular domain family. Conclusions: CLAP is a useful protein-clustering tool, independent of domain assignment, domain order, sequence length and domain diversity. Our method can be used for any set of protein sequences, yielding functionally relevant clusters with high domain architectural homogeneity. The CLAP web server is freely available for academic use at http://nslab.mbu.iisc.ernet.in/clap/. [ABSTRACT FROM AUTHOR]

Background: Amino acid sequences and features extracted from such sequences have been used to predict many protein properties, such as subcellular localization or solubility, using classifier algorithms. Although software tools are available for both feature extraction and classifier construction, their application is not straightforward, requiring users to install various packages and to convert data into different formats. This lack of easily accessible software hampers quick, explorative use of sequence-based classification techniques by biologists. Results: We have developed the web-based software tool SPiCE for exploring sequence-based features of proteins in predefined classes. It offers data upload/download, sequence-based feature calculation, data visualization and protein classifier construction and testing in a single integrated, interactive environment. To illustrate its use, two example datasets are included showing the identification of differences in amino acid composition between proteins yielding low and high production levels in fungi and low and high expression levels in yeast, respectively. Conclusions: SPiCE is an easy-to-use online tool for extracting and exploring sequence-based features of sets of proteins, allowing non-experts to apply advanced classification techniques. The tool is available at http://helix.ewi. tudelft.nl/spice. [ABSTRACT FROM AUTHOR]