The Resource Description Framework (RDF), together with well-defined ontologies, significantly in... more The Resource Description Framework (RDF), together with well-defined ontologies, significantly increases data interoperability and usability. The SPARQL query language was introduced to retrieve requested RDF data and to explore links between them. Among other useful features, SPARQL supports federated queries that combine multiple independent data source endpoints. This allows users to obtain insights that are not possible using only a single data source. Owing to all of these useful features, many biological and chemical databases present their data in RDF, and support SPARQL querying. In our project, we primary focused on PubChem, ChEMBL and ChEBI small-molecule datasets. These datasets are already being exported to RDF by their creators. However, none of them has an official and currently supported SPARQL endpoint. This omission makes it difficult to construct complex or federated queries that could access all of the datasets, thus underutilising the main advantage of the availa...
SimTandem is a tool for fast identification of protein and peptide sequences from tandem mass spe... more SimTandem is a tool for fast identification of protein and peptide sequences from tandem mass spectra. The identification is based on similarity search of spectra captured by a tandem mass spectrometer in databases of theoretical mass spectra generated from databases of known protein sequences. Since the number of protein sequences in the databases grows rapidly and a sequential scan over the entire database of spectra is time-consuming, the non-metric access methods are employed as the database indexing ...
Interactions among amino acid residues are the principal contributor to the stability of the thre... more Interactions among amino acid residues are the principal contributor to the stability of the three-dimensional structure of a protein. The Amino Acid Interactions (INTAA) web server (https://bioinfo.uochb.cas.cz/INTAA/) has established itself as a unique computational resource, which enables users to calculate the contribution of individual residues in a biomolecular structure to its total energy using a molecular mechanical scoring function. In this update, we describe major additions to the web server which help solidify its position as a robust, comprehensive resource for biomolecular structure analysis. Importantly, a new continuum solvation model was introduced, allowing more accurate representation of electrostatic interactions in aqueous media. In addition, a low-overhead pipeline for the estimation of evolutionary conservation in protein chains has been added. New visualization options were introduced as well, allowing users to easily switch between and interrelate the energ...
Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge man... more Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges to data access, either within the discipline or to integration and interoperability between related domains. The fundamental elements of exchange are referenced structure-organism pairs that establish relationships between distinct molecular structures and the living organisms from which they were identified. Consolidating and sharing such information via an open platform has strong transformative potential for natural products research and beyond. This is the ultimate goal of the newly established LOTUS initiative, which has now completed the first steps toward the harmonization, curation, validation and open dissemination of 700,000+ referenced structure-organism pairs. LOTUS data is hos...
It was highlighted that the original article [1] contained an error in the last paragraph of the ... more It was highlighted that the original article [1] contained an error in the last paragraph of the section ‘Structure search using SPARQL’, specifically in the radius of the used fingerprint. This Correction article shows the incorrect and correct paragraph of this section.
Motivation The existing connections between large databases of chemicals, proteins, metabolites a... more Motivation The existing connections between large databases of chemicals, proteins, metabolites and assays offer valuable resources for research in fields ranging from drug design to metabolomics. Transparent search across multiple databases provides a way to efficiently utilize these resources. To simplify such searches, many databases have adopted semantic technologies that allow interoperable querying of the datasets using SPARQL query language. However, the interoperable interfaces of the chemical databases still lack the functionality of structure-driven chemical search, which is a fundamental method of data discovery in the chemical search space. Results We present a SPARQL service that augments existing semantic services by making interoperable substructure and similarity searches in small-molecule databases possible. The service thus offers new possibilities for querying interoperable databases, and simplifies writing of heterogeneous queries that include chemical-structure ...
Background: Structure search is one of the valuable capabilities of small-molecule databases. Fin... more Background: Structure search is one of the valuable capabilities of small-molecule databases. Fingerprint-based screening methods are usually employed to enhance the search performance by reducing the number of calls to the verification procedure. In substructure search, fingerprints are designed to capture important structural aspects of the molecule to aid the decision about whether the molecule contains a given substructure. Currently available cartridges typically provide acceptable search performance for processing user queries, but do not scale satisfactorily with dataset size. Results: We present Sachem, a new open-source chemical cartridge that implements two substructure search methods: The first is a performance-oriented reimplementation of substructure indexing based on the OrChem fingerprint, and the second is a novel method that employs newly designed fingerprints stored in inverted indices. We assessed the performance of both methods on small, medium, and large datasets containing 1, 10, and 94 million compounds, respectively. Comparison of Sachem with other freely available cartridges revealed improvements in overall performance, scaling potential and screen-out efficiency. Conclusions: The Sachem cartridge allows efficient substructure searches in databases of all sizes. The sublinear performance scaling of the second method and the ability to efficiently query large amounts of pre-extracted information may together open the door to new applications for substructure searches.
Large biomolecules-proteins and nucleic acids-are composed of building blocks which define their ... more Large biomolecules-proteins and nucleic acids-are composed of building blocks which define their identity, properties and binding capabilities. In order to shed light on the energetic side of interactions of amino acids between themselves and with deoxyribonucleotides, we present the Amino Acid Interaction web server (http://bioinfo.uochb.cas.cz/INTAA/). INTAA offers the calculation of the residue Interaction Energy Matrix for any protein structure (deposited in Protein Data Bank or submitted by the user) and a comprehensive analysis of the interfaces in protein-DNA complexes. The Interaction Energy Matrix web application aims to identify key residues within protein structures which contribute significantly to the stability of the protein. The application provides an interactive user interface enhanced by 3D structure viewer for efficient visualization of pairwise and net interaction energies of individual amino acids, side chains and backbones. The protein-DNA interaction analysis part of the web server allows the user to view the relative abundance of various configurations of amino acid-deoxyribonucleotide pairs found at the protein-DNA interface and the interaction energies corresponding to these configurations calculated using a molecular mechanical force field. The effects of the sugar-phosphate moiety and of the dielectric properties of the solvent on the interaction energies can be studied for the various configurations.
ABSTRACT In order to realize the idea of the Semantic Web, many tools and technologies need to be... more ABSTRACT In order to realize the idea of the Semantic Web, many tools and technologies need to be developed, including a query language. One of the most important technologies that creates a base for the Semantic Web is the RDF (Resource Description Framework). There are many query languages for the RDF, but almost all of them are very weak and they can not be used for a general purpose. In this paper, we introduce the Tequila query language, developed for the recently introduced Trisolda infrastructure for the Semantic Web. In particular, we describe the syntax and semantics of the Tequila language and we show usage of this language and its power on several examples. The examples show how to convert a RDF Collection into a RDF Bag or how to evaluate an aggregation function (e.g., maximum of values) without the need of a built-in support. Unlike almost all other query languages, Tequila is powerful enough to express both of the tasks.
Abstract We have generalized a method for tandem mass spectra interpretation, based on the parame... more Abstract We have generalized a method for tandem mass spectra interpretation, based on the parameterized Hausdorff distance d HP. Instead of just peptides (short pieces of proteins), in this paper we describe the interpretation of whole protein sequences. For this purpose, we employ the recently introduced NM-tree to index the database of hypothetical mass spectra for exact or fast approximate search. The NM-tree combines the M-tree with the TriGen algorithm in a way that allows to dynamically control the retrieval precision at ...
Abstract. Even though the semantic web become actual topic of research recently, there are no com... more Abstract. Even though the semantic web become actual topic of research recently, there are no complex solutions for building semantic applications yet to our best knowledge. We describe a complex architecture which covers storing, querying, manipulation and visualization of semantic data in a programmer-friendly way. The architecture is currently being applied in a real-life web portal. Keywords: semantic, web, RDF, web services, XML
Background: In recent years, the Resource Description Framework (RDF) and the SPARQL query langua... more Background: In recent years, the Resource Description Framework (RDF) and the SPARQL query language have become more widely used in the area of cheminformatics and bioinformatics databases. These technologies allow better interoperability of various data sources and powerful searching facilities. However, we identified several deficiencies that make usage of such RDF databases restrictive or challenging for common users. Results: We extended a SPARQL engine to be able to use special procedures inside SPARQL queries. This allows the user to work with data that cannot be simply precomputed and thus cannot be directly stored in the database. We designed an algorithm that checks a query against data ontology to identify possible user errors. This greatly improves query debugging. We also introduced an approach to visualize retrieved data in a user-friendly way, based on templates describing visualizations of resource classes. To integrate all of our approaches, we developed a simple web application. Conclusions: Our system was implemented successfully, and we demonstrated its usability on the ChEBI database transformed into RDF form. To demonstrate procedure call functions, we employed compound similarity searching based on OrChem. The application is publicly available at https://bioinfo.uochb.cas.cz/projects/chemRDF.
Cancer is after cardiovascular disease the most frequent cause of death in Europe. In 28 of 53 co... more Cancer is after cardiovascular disease the most frequent cause of death in Europe. In 28 of 53 countries considered in this area it is already the leading cause of death and expected to gain even more importance until the year 2020. Amongst the large arsenal of different anti-cancer drugs, platinum drugs belong to the first developed anticancer drugs and still have a large impact on cancer therapy. Nevertheless therapy with platinum-anticancer drugs is accompanied by severe adverse effects caused by frequent interactions with the amino acids of different human proteins. Computational chemistry offers methods to study such interactions and even those of not yet synthesized drugs in silico. For such studies a profound knowledge of the prediction quality of various computational methods towards platinum-drug-like complexes is necessary. By this article we are aiming on delivering important accuracy information of the frequently used computational methods. Most important findings are the high performance of the double hybrid functional B2PLYP for the calculation of geometries, even in small basis sets, followed by BP86 and PBE and the still acceptable performance of the semi-empirical Method PM6-D3H4X for extremely large systems. To follow absolute energies of the dissociation process, LPNO-CEPA and B3LYP-D3 can be suggested while SCS-MP2 shows an extremely narrow standard deviation and a low maximum error, which make it an ideal candidate for relative energy calculations in the exploration of reaction mechanisms.
Background: There are many databases of small molecules focused on different aspects of research ... more Background: There are many databases of small molecules focused on different aspects of research and its applications. Some tasks may require integration of information from various databases. However, determining which entries from different databases represent the same compound is not straightforward. Integration can be based, for example, on automatically generated cross-reference links between entries. Another approach is to use the manually curated links stored directly in databases. This study employs well-established InChI identifiers to measure the consistency and completeness of the manually curated links by comparing them with the automatically generated ones.
Results: We used two different tools to generate InChI identifiers and observed some ambiguities in their outputs. In part, these ambiguities were caused by indistinctness in interpretation of the structural data used. InChI identifiers were used successfully to find duplicate entries in databases. We found that the InChI inconsistencies in the manually curated links are very high (28.85% in the worst case). Even using a weaker definition of consistency, the measured values were very high in general. The completeness of the manually curated links was also very poor (only 93.8% in the best case) compared with that of the automatically generated links.
Conclusions: We observed several problems with the InChI tools and the files used as their inputs. There are large gaps in the consistency and completeness of manually curated links if they are measured using InChI identifiers. However, inconsistency can be caused both by errors in manually curated links and the inherent limitations of the InChI method.
Background: Similarity search in protein databases is one of the most essential issues in computa... more Background: Similarity search in protein databases is one of the most essential issues in computational proteomics. With the growing number of experimentally resolved protein structures, the focus shifted from sequences to structures. The area of structure similarity forms a big challenge since even no standard definition of optimal structure similarity exists in the field.
Results: We propose a protein structure similarity measure called SProt. SProt concentrates on high-quality modeling of local similarity in the process of feature extraction. SProt’s features are based on spherical spatial neighborhood of amino acids where similarity can be well-defined. On top of the partial local similarities, global measure assessing similarity to a pair of protein structures is built. Finally, indexing is applied making the search process by an order of magnitude faster.
Conclusions: The proposed method outperforms other methods in classification accuracy on SCOP superfamily and fold level, while it is at least comparable to the best existing solutions in terms of precision-recall or quality of alignment.
Similarity search in protein structure databases is an important task of computational biology. T... more Similarity search in protein structure databases is an important task of computational biology. To reduce the time required to search for similar structures, indexing techniques are being often introduced. However, as the indexing phase is computationally very expensive, it becomes useful only when a large number of searches are expected (so that the expensive indexing cost is amortized by cheaper search cost). This is a typical situation for a public similarity search service. In this article we introduce the P3S web application ( http://siret.cz/p3s ) allowing, given a query structure, to identify the set of the most similar structures in a database. The result set can be browsed interactively, including visual inspection of the structure superposition, or it can be downloaded as a zip archive. P3S employs the SProt similarity measure and an indexing technique based on the LAESA method, both introduced recently by our group. Together with the measure and the index, the method presents an effective and efficient tool for querying protein structure databases.
Similarity measures for the protein structures are quite complex and require significant computat... more Similarity measures for the protein structures are quite complex and require significant computational time. We propose a parallel approach to this problem to fully exploit the computational power of current CPU architectures. This paper summarizes experience and insights acquired from the parallel implementation of the SProt similarity method, its database access method, and also the wellknown TM-score algorithm. The implementation scales almost linearly with the number of CPUs and achieves 21.4× speedup on a 24-core system. The implementation is currently employed in the web application http://siret.cz/p3s.
Protein structure similarity search is one of the most essential tasks in current proteomics. Wit... more Protein structure similarity search is one of the most essential tasks in current proteomics. With the growing number of experimentally solved protein structures, the need for accurate and fast search methods is increasing. We have recently introduced similarity measure SProt showing good results in terms of effectiveness. However, this measure is computationally very intensive and, moreover, it is not suitable for metric indexing. In this paper, we introduce an efficient metric approximation of the SProt measure maintaining its former effectiveness.
The Resource Description Framework (RDF), together with well-defined ontologies, significantly in... more The Resource Description Framework (RDF), together with well-defined ontologies, significantly increases data interoperability and usability. The SPARQL query language was introduced to retrieve requested RDF data and to explore links between them. Among other useful features, SPARQL supports federated queries that combine multiple independent data source endpoints. This allows users to obtain insights that are not possible using only a single data source. Owing to all of these useful features, many biological and chemical databases present their data in RDF, and support SPARQL querying. In our project, we primary focused on PubChem, ChEMBL and ChEBI small-molecule datasets. These datasets are already being exported to RDF by their creators. However, none of them has an official and currently supported SPARQL endpoint. This omission makes it difficult to construct complex or federated queries that could access all of the datasets, thus underutilising the main advantage of the availa...
SimTandem is a tool for fast identification of protein and peptide sequences from tandem mass spe... more SimTandem is a tool for fast identification of protein and peptide sequences from tandem mass spectra. The identification is based on similarity search of spectra captured by a tandem mass spectrometer in databases of theoretical mass spectra generated from databases of known protein sequences. Since the number of protein sequences in the databases grows rapidly and a sequential scan over the entire database of spectra is time-consuming, the non-metric access methods are employed as the database indexing ...
Interactions among amino acid residues are the principal contributor to the stability of the thre... more Interactions among amino acid residues are the principal contributor to the stability of the three-dimensional structure of a protein. The Amino Acid Interactions (INTAA) web server (https://bioinfo.uochb.cas.cz/INTAA/) has established itself as a unique computational resource, which enables users to calculate the contribution of individual residues in a biomolecular structure to its total energy using a molecular mechanical scoring function. In this update, we describe major additions to the web server which help solidify its position as a robust, comprehensive resource for biomolecular structure analysis. Importantly, a new continuum solvation model was introduced, allowing more accurate representation of electrostatic interactions in aqueous media. In addition, a low-overhead pipeline for the estimation of evolutionary conservation in protein chains has been added. New visualization options were introduced as well, allowing users to easily switch between and interrelate the energ...
Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge man... more Contemporary bioinformatic and chemoinformatic capabilities hold promise to reshape knowledge management, analysis and interpretation of data in natural products research. Currently, reliance on a disparate set of non-standardized, insular, and specialized databases presents a series of challenges to data access, either within the discipline or to integration and interoperability between related domains. The fundamental elements of exchange are referenced structure-organism pairs that establish relationships between distinct molecular structures and the living organisms from which they were identified. Consolidating and sharing such information via an open platform has strong transformative potential for natural products research and beyond. This is the ultimate goal of the newly established LOTUS initiative, which has now completed the first steps toward the harmonization, curation, validation and open dissemination of 700,000+ referenced structure-organism pairs. LOTUS data is hos...
It was highlighted that the original article [1] contained an error in the last paragraph of the ... more It was highlighted that the original article [1] contained an error in the last paragraph of the section ‘Structure search using SPARQL’, specifically in the radius of the used fingerprint. This Correction article shows the incorrect and correct paragraph of this section.
Motivation The existing connections between large databases of chemicals, proteins, metabolites a... more Motivation The existing connections between large databases of chemicals, proteins, metabolites and assays offer valuable resources for research in fields ranging from drug design to metabolomics. Transparent search across multiple databases provides a way to efficiently utilize these resources. To simplify such searches, many databases have adopted semantic technologies that allow interoperable querying of the datasets using SPARQL query language. However, the interoperable interfaces of the chemical databases still lack the functionality of structure-driven chemical search, which is a fundamental method of data discovery in the chemical search space. Results We present a SPARQL service that augments existing semantic services by making interoperable substructure and similarity searches in small-molecule databases possible. The service thus offers new possibilities for querying interoperable databases, and simplifies writing of heterogeneous queries that include chemical-structure ...
Background: Structure search is one of the valuable capabilities of small-molecule databases. Fin... more Background: Structure search is one of the valuable capabilities of small-molecule databases. Fingerprint-based screening methods are usually employed to enhance the search performance by reducing the number of calls to the verification procedure. In substructure search, fingerprints are designed to capture important structural aspects of the molecule to aid the decision about whether the molecule contains a given substructure. Currently available cartridges typically provide acceptable search performance for processing user queries, but do not scale satisfactorily with dataset size. Results: We present Sachem, a new open-source chemical cartridge that implements two substructure search methods: The first is a performance-oriented reimplementation of substructure indexing based on the OrChem fingerprint, and the second is a novel method that employs newly designed fingerprints stored in inverted indices. We assessed the performance of both methods on small, medium, and large datasets containing 1, 10, and 94 million compounds, respectively. Comparison of Sachem with other freely available cartridges revealed improvements in overall performance, scaling potential and screen-out efficiency. Conclusions: The Sachem cartridge allows efficient substructure searches in databases of all sizes. The sublinear performance scaling of the second method and the ability to efficiently query large amounts of pre-extracted information may together open the door to new applications for substructure searches.
Large biomolecules-proteins and nucleic acids-are composed of building blocks which define their ... more Large biomolecules-proteins and nucleic acids-are composed of building blocks which define their identity, properties and binding capabilities. In order to shed light on the energetic side of interactions of amino acids between themselves and with deoxyribonucleotides, we present the Amino Acid Interaction web server (http://bioinfo.uochb.cas.cz/INTAA/). INTAA offers the calculation of the residue Interaction Energy Matrix for any protein structure (deposited in Protein Data Bank or submitted by the user) and a comprehensive analysis of the interfaces in protein-DNA complexes. The Interaction Energy Matrix web application aims to identify key residues within protein structures which contribute significantly to the stability of the protein. The application provides an interactive user interface enhanced by 3D structure viewer for efficient visualization of pairwise and net interaction energies of individual amino acids, side chains and backbones. The protein-DNA interaction analysis part of the web server allows the user to view the relative abundance of various configurations of amino acid-deoxyribonucleotide pairs found at the protein-DNA interface and the interaction energies corresponding to these configurations calculated using a molecular mechanical force field. The effects of the sugar-phosphate moiety and of the dielectric properties of the solvent on the interaction energies can be studied for the various configurations.
ABSTRACT In order to realize the idea of the Semantic Web, many tools and technologies need to be... more ABSTRACT In order to realize the idea of the Semantic Web, many tools and technologies need to be developed, including a query language. One of the most important technologies that creates a base for the Semantic Web is the RDF (Resource Description Framework). There are many query languages for the RDF, but almost all of them are very weak and they can not be used for a general purpose. In this paper, we introduce the Tequila query language, developed for the recently introduced Trisolda infrastructure for the Semantic Web. In particular, we describe the syntax and semantics of the Tequila language and we show usage of this language and its power on several examples. The examples show how to convert a RDF Collection into a RDF Bag or how to evaluate an aggregation function (e.g., maximum of values) without the need of a built-in support. Unlike almost all other query languages, Tequila is powerful enough to express both of the tasks.
Abstract We have generalized a method for tandem mass spectra interpretation, based on the parame... more Abstract We have generalized a method for tandem mass spectra interpretation, based on the parameterized Hausdorff distance d HP. Instead of just peptides (short pieces of proteins), in this paper we describe the interpretation of whole protein sequences. For this purpose, we employ the recently introduced NM-tree to index the database of hypothetical mass spectra for exact or fast approximate search. The NM-tree combines the M-tree with the TriGen algorithm in a way that allows to dynamically control the retrieval precision at ...
Abstract. Even though the semantic web become actual topic of research recently, there are no com... more Abstract. Even though the semantic web become actual topic of research recently, there are no complex solutions for building semantic applications yet to our best knowledge. We describe a complex architecture which covers storing, querying, manipulation and visualization of semantic data in a programmer-friendly way. The architecture is currently being applied in a real-life web portal. Keywords: semantic, web, RDF, web services, XML
Background: In recent years, the Resource Description Framework (RDF) and the SPARQL query langua... more Background: In recent years, the Resource Description Framework (RDF) and the SPARQL query language have become more widely used in the area of cheminformatics and bioinformatics databases. These technologies allow better interoperability of various data sources and powerful searching facilities. However, we identified several deficiencies that make usage of such RDF databases restrictive or challenging for common users. Results: We extended a SPARQL engine to be able to use special procedures inside SPARQL queries. This allows the user to work with data that cannot be simply precomputed and thus cannot be directly stored in the database. We designed an algorithm that checks a query against data ontology to identify possible user errors. This greatly improves query debugging. We also introduced an approach to visualize retrieved data in a user-friendly way, based on templates describing visualizations of resource classes. To integrate all of our approaches, we developed a simple web application. Conclusions: Our system was implemented successfully, and we demonstrated its usability on the ChEBI database transformed into RDF form. To demonstrate procedure call functions, we employed compound similarity searching based on OrChem. The application is publicly available at https://bioinfo.uochb.cas.cz/projects/chemRDF.
Cancer is after cardiovascular disease the most frequent cause of death in Europe. In 28 of 53 co... more Cancer is after cardiovascular disease the most frequent cause of death in Europe. In 28 of 53 countries considered in this area it is already the leading cause of death and expected to gain even more importance until the year 2020. Amongst the large arsenal of different anti-cancer drugs, platinum drugs belong to the first developed anticancer drugs and still have a large impact on cancer therapy. Nevertheless therapy with platinum-anticancer drugs is accompanied by severe adverse effects caused by frequent interactions with the amino acids of different human proteins. Computational chemistry offers methods to study such interactions and even those of not yet synthesized drugs in silico. For such studies a profound knowledge of the prediction quality of various computational methods towards platinum-drug-like complexes is necessary. By this article we are aiming on delivering important accuracy information of the frequently used computational methods. Most important findings are the high performance of the double hybrid functional B2PLYP for the calculation of geometries, even in small basis sets, followed by BP86 and PBE and the still acceptable performance of the semi-empirical Method PM6-D3H4X for extremely large systems. To follow absolute energies of the dissociation process, LPNO-CEPA and B3LYP-D3 can be suggested while SCS-MP2 shows an extremely narrow standard deviation and a low maximum error, which make it an ideal candidate for relative energy calculations in the exploration of reaction mechanisms.
Background: There are many databases of small molecules focused on different aspects of research ... more Background: There are many databases of small molecules focused on different aspects of research and its applications. Some tasks may require integration of information from various databases. However, determining which entries from different databases represent the same compound is not straightforward. Integration can be based, for example, on automatically generated cross-reference links between entries. Another approach is to use the manually curated links stored directly in databases. This study employs well-established InChI identifiers to measure the consistency and completeness of the manually curated links by comparing them with the automatically generated ones.
Results: We used two different tools to generate InChI identifiers and observed some ambiguities in their outputs. In part, these ambiguities were caused by indistinctness in interpretation of the structural data used. InChI identifiers were used successfully to find duplicate entries in databases. We found that the InChI inconsistencies in the manually curated links are very high (28.85% in the worst case). Even using a weaker definition of consistency, the measured values were very high in general. The completeness of the manually curated links was also very poor (only 93.8% in the best case) compared with that of the automatically generated links.
Conclusions: We observed several problems with the InChI tools and the files used as their inputs. There are large gaps in the consistency and completeness of manually curated links if they are measured using InChI identifiers. However, inconsistency can be caused both by errors in manually curated links and the inherent limitations of the InChI method.
Background: Similarity search in protein databases is one of the most essential issues in computa... more Background: Similarity search in protein databases is one of the most essential issues in computational proteomics. With the growing number of experimentally resolved protein structures, the focus shifted from sequences to structures. The area of structure similarity forms a big challenge since even no standard definition of optimal structure similarity exists in the field.
Results: We propose a protein structure similarity measure called SProt. SProt concentrates on high-quality modeling of local similarity in the process of feature extraction. SProt’s features are based on spherical spatial neighborhood of amino acids where similarity can be well-defined. On top of the partial local similarities, global measure assessing similarity to a pair of protein structures is built. Finally, indexing is applied making the search process by an order of magnitude faster.
Conclusions: The proposed method outperforms other methods in classification accuracy on SCOP superfamily and fold level, while it is at least comparable to the best existing solutions in terms of precision-recall or quality of alignment.
Similarity search in protein structure databases is an important task of computational biology. T... more Similarity search in protein structure databases is an important task of computational biology. To reduce the time required to search for similar structures, indexing techniques are being often introduced. However, as the indexing phase is computationally very expensive, it becomes useful only when a large number of searches are expected (so that the expensive indexing cost is amortized by cheaper search cost). This is a typical situation for a public similarity search service. In this article we introduce the P3S web application ( http://siret.cz/p3s ) allowing, given a query structure, to identify the set of the most similar structures in a database. The result set can be browsed interactively, including visual inspection of the structure superposition, or it can be downloaded as a zip archive. P3S employs the SProt similarity measure and an indexing technique based on the LAESA method, both introduced recently by our group. Together with the measure and the index, the method presents an effective and efficient tool for querying protein structure databases.
Similarity measures for the protein structures are quite complex and require significant computat... more Similarity measures for the protein structures are quite complex and require significant computational time. We propose a parallel approach to this problem to fully exploit the computational power of current CPU architectures. This paper summarizes experience and insights acquired from the parallel implementation of the SProt similarity method, its database access method, and also the wellknown TM-score algorithm. The implementation scales almost linearly with the number of CPUs and achieves 21.4× speedup on a 24-core system. The implementation is currently employed in the web application http://siret.cz/p3s.
Protein structure similarity search is one of the most essential tasks in current proteomics. Wit... more Protein structure similarity search is one of the most essential tasks in current proteomics. With the growing number of experimentally solved protein structures, the need for accurate and fast search methods is increasing. We have recently introduced similarity measure SProt showing good results in terms of effectiveness. However, this measure is computationally very intensive and, moreover, it is not suitable for metric indexing. In this paper, we introduce an efficient metric approximation of the SProt measure maintaining its former effectiveness.
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Papers by Jakub Galgonek
Results: We used two different tools to generate InChI identifiers and observed some ambiguities in their outputs. In part, these ambiguities were caused by indistinctness in interpretation of the structural data used. InChI identifiers were used successfully to find duplicate entries in databases. We found that the InChI inconsistencies in the manually curated links are very high (28.85% in the worst case). Even using a weaker definition of consistency, the measured values were very high in general. The completeness of the manually curated links was also very poor (only 93.8% in the best case) compared with that of the automatically generated links.
Conclusions: We observed several problems with the InChI tools and the files used as their inputs. There are large gaps in the consistency and completeness of manually curated links if they are measured using InChI identifiers. However, inconsistency can be caused both by errors in manually curated links and the inherent limitations of the InChI method.
Results: We propose a protein structure similarity measure called SProt. SProt concentrates on high-quality modeling of local similarity in the process of feature extraction. SProt’s features are based on spherical spatial neighborhood of amino acids where similarity can be well-defined. On top of the partial local similarities, global measure assessing similarity to a pair of protein structures is built. Finally, indexing is applied making the search process by an order of magnitude faster.
Conclusions: The proposed method outperforms other methods in classification accuracy on SCOP superfamily and fold level, while it is at least comparable to the best existing solutions in terms of precision-recall or quality of alignment.
Results: We used two different tools to generate InChI identifiers and observed some ambiguities in their outputs. In part, these ambiguities were caused by indistinctness in interpretation of the structural data used. InChI identifiers were used successfully to find duplicate entries in databases. We found that the InChI inconsistencies in the manually curated links are very high (28.85% in the worst case). Even using a weaker definition of consistency, the measured values were very high in general. The completeness of the manually curated links was also very poor (only 93.8% in the best case) compared with that of the automatically generated links.
Conclusions: We observed several problems with the InChI tools and the files used as their inputs. There are large gaps in the consistency and completeness of manually curated links if they are measured using InChI identifiers. However, inconsistency can be caused both by errors in manually curated links and the inherent limitations of the InChI method.
Results: We propose a protein structure similarity measure called SProt. SProt concentrates on high-quality modeling of local similarity in the process of feature extraction. SProt’s features are based on spherical spatial neighborhood of amino acids where similarity can be well-defined. On top of the partial local similarities, global measure assessing similarity to a pair of protein structures is built. Finally, indexing is applied making the search process by an order of magnitude faster.
Conclusions: The proposed method outperforms other methods in classification accuracy on SCOP superfamily and fold level, while it is at least comparable to the best existing solutions in terms of precision-recall or quality of alignment.