The Literature of Chemoinformatics: 1978-2018.

This article presents a study of the literature of chemoinformatics, updating and building upon an analogous bibliometric investigation that was published in 2008. Data on outputs in the field, and citations to those outputs, were obtained by means of topic searches of the Web of Science Core Collection. The searches demonstrate that chemoinformatics is by now a well-defined sub-discipline of chemistry, and one that forms an essential part of the chemical educational curriculum. There are three core journals for the subject: The Journal of Chemical Information and Modeling, the Journal of Cheminformatics, and Molecular Informatics, and, having established itself, chemoinformatics is now starting to export knowledge to disciplines outside of chemistry.

COGNAC: a web server for searching and annotating hydrogen-bonded base interactions in RNA three-dimensional structures.

Hydrogen bonds are crucial factors that stabilize a complex ribonucleic acid (RNA) molecule's three-dimensional (3D) structure. Minute conformational changes can result in variations in the hydrogen bond interactions in a particular structure. Furthermore, networks of hydrogen bonds, especially those found in tight clusters, may be important elements in structure stabilization or function and can therefore be regarded as potential tertiary motifs. In this paper, we describe a graph theoretical algorithm implemented as a web server that is able to search for unbroken networks of hydrogen-bonded base interactions and thus provide an accounting of such interactions in RNA 3D structures. This server, COGNAC (COnnection tables Graphs for Nucleic ACids), is also able to compare the hydrogen bond networks between two structures and from such annotations enable the mapping of atomic level differences that may have resulted from conformational changes due to mutations or binding events. The COGNAC server can be accessed at http://mfrlab.org/grafss/cognac.

Special Issue: Chemoinformatics.

Chemoinformatics techniques were originally developed for the construction and searching of large archives of chemical structures but they were soon applied to problems in drug discovery and are now playing an increasingly important role in many additional areas of chemistry. This Special Issue contains seven original research articles and four review articles that provide an introduction to several aspects of this rapidly developing field.

Maximum common substructure-based data fusion in similarity searching.

Data fusion has been shown to work very well when applied to fingerprint-based similarity searching, yet little is known of its application to maximum common substructure (MCS)-based similarity searching. Two similarity search applications of the MCS will be focused on here. Typically, the number of bonds in the MCS, as well as the bonds in the two molecules being compared, are used in a similarity coefficient. The power of this technique can be extended using data fusion, where the MCS similarities of a set of reference molecules against one database molecule are fused. This "group fusion" technique forms the first application of the MCS in this work. The other application is that of the chemical hyperstructure. The hyperstructure concept is an alternative form of data fusion, being a hypothetical molecule that is constructed from the overlap of a set of existing molecules. This paper compares fingerprint group fusion (extended-connectivity fingerprints), MCS similarity group fusion, and hyperstructure similarity searching, and describes their relative merits and complementarity in virtual screening. It is concluded that the hyperstructure approach as implemented here is less generally effective than conventional fingerprint approaches.

Calculation of substructural analysis weights using a genetic algorithm.

This work describes a genetic algorithm for the calculation of substructural analysis for use in ligand-based virtual screening. The algorithm is simple in concept and effective in operation, with simulated virtual screening experiments using the MDDR and WOMBAT data sets showing it to be superior to substructural analysis weights based on a naive Bayesian classifier.

IMAAAGINE: a webserver for searching hypothetical 3D amino acid side chain arrangements in the Protein Data Bank.

We describe a server that allows the interrogation of the Protein Data Bank for hypothetical 3D side chain patterns that are not limited to known patterns from existing 3D structures. A minimal side chain description allows a variety of side chain orientations to exist within the pattern, and generic side chain types such as acid, base and hydroxyl-containing can be additionally deployed in the search query. Moreover, only a subset of distances between the side chains need be specified. We illustrate these capabilities in case studies involving arginine stacks, serine-acid group arrangements and multiple catalytic triad-like configurations. The IMAAAGINE server can be accessed at http://mfrlab.org/grafss/imaaagine/.

NASSAM: a server to search for and annotate tertiary interactions and motifs in three-dimensional structures of complex RNA molecules.

Similarities in the 3D patterns of RNA base interactions or arrangements can provide insights into their functions and roles in stabilization of the RNA 3D structure. Nucleic Acids Search for Substructures and Motifs (NASSAM) is a graph theoretical program that can search for 3D patterns of base arrangements by representing the bases as pseudo-atoms. The geometric relationship of the pseudo-atoms to each other as a pattern can be represented as a labeled graph where the pseudo-atoms are the graph's nodes while the edges are the inter-pseudo-atomic distances. The input files for NASSAM are PDB formatted 3D coordinates. This web server can be used to identify matches of base arrangement patterns in a query structure to annotated patterns that have been reported in the literature or that have possible functional and structural stabilization implications. The NASSAM program is freely accessible without any login requirement at http://mfrlab.org/grafss/nassam/.

SPRITE and ASSAM: web servers for side chain 3D-motif searching in protein structures.

Similarities in the 3D patterns of amino acid side chains can provide insights into their function despite the absence of any detectable sequence or fold similarities. Search for protein sites (SPRITE) and amino acid pattern search for substructures and motifs (ASSAM) are graph theoretical programs that can search for 3D amino side chain matches in protein structures, by representing the amino acid side chains as pseudo-atoms. The geometric relationship of the pseudo-atoms to each other as a pattern can be represented as a labeled graph where the pseudo-atoms are the graph's nodes while the edges are the inter-pseudo-atomic distances. Both programs require the input file to be in the PDB format. The objective of using SPRITE is to identify matches of side chains in a query structure to patterns with characterized function. In contrast, a 3D pattern of interest can be searched for existing occurrences in available PDB structures using ASSAM. Both programs are freely accessible without any login requirement. SPRITE is available at http://mfrlab.org/grafss/sprite/ while ASSAM can be accessed at http://mfrlab.org/grafss/assam/.

Scholarly communication between health informatics and information systems: A bibliometric study.

The challenges of IT adoption in the healthcare sector have generated much interest across a range of research communities, including Information Systems (IS) and Health Informatics (HI). Given their long-standing interest in IT design, development, implementation, and adoption to improve productivity and support organisational transformation, the IS and HI fields are highly correlated in their research interests. Nevertheless, the two fields serve different academic audiences, have different research foci, and theorise IT artifacts differently. We investigate the dyadic relationship between health information systems (HIS) research in IS and HI through the communication patterns between the two fields. We present the citation analysis results of HIS research published in IS and HI journals between 2000 and 2020. The results revealed that despite the two fields sharing a common interest, communication between them is limited and only about specific topics. Potentially relevant ideas and theories generated in IS have not yet been sufficiently recognised by HI scholars and incorporated into the HI literature. However, the upward trend of HIS publications in IS indicates that IS has the potential to contribute more to HI.

Similarity coefficients for binary chemoinformatics data: overview and extended comparison using simulated and real data sets.

This paper reports an analysis and comparison of the use of 51 different similarity coefficients for computing the similarities between binary fingerprints for both simulated and real chemical data sets. Five pairs and a triplet of coefficients were found to yield identical similarity values, leading to the elimination of seven of the coefficients. The remaining 44 coefficients were then compared in two ways: by their theoretical characteristics using simple descriptive statistics, correlation analysis, multidimensional scaling, Hasse diagrams, and the recently described atemporal target diffusion model; and by their effectiveness for similarity-based virtual screening using MDDR, WOMBAT, and MUV data. The comparisons demonstrate the general utility of the well-known Tanimoto method but also suggest other coefficients that may be worthy of further attention.

The Journal of Computer-Aided Molecular Design: a bibliometric note.

Summarizes the articles in, and the citations to, volumes 2-24 of the Journal of Computer-Aided Molecular Design. The citations to the journal come from almost 2000 different sources that span a very wide range of academic subjects, with the most heavily cited articles being descriptions of software systems and of computational methods.

Combining multiple classifications of chemical structures using consensus clustering.

Consensus clustering involves combining multiple clusterings of the same set of objects to achieve a single clustering that will, hopefully, provide a better picture of the groupings that are present in a dataset. This Letter reports the use of consensus clustering methods on sets of chemical compounds represented by 2D fingerprints. Experiments with DUD, IDAlert, MDDR and MUV data suggests that consensus methods are unlikely to result in significant improvements in clustering effectiveness as compared to the use of a single clustering method.

Commentary: the first twelve years of the Journal of chemoinformatics.

This commentary provides an overview of the publications in, and the citations to, the first twelve volumes of the Journal of Cheminformatics, covering the period 2009-2020. The analysis is based on the 622 articles that have appeared in the journal during that time and that have been indexed in the Clarivate Web of Science Core Collection database. It is clear that the journal has established itself as one of the most important publications in the field of cheminformatics: it attracts citations not only from other journals in its specialist field but also from biological and chemical journals more widely, and moreover from journals that are far removed in focus from it but that are still able to benefit from the articles that it publishes.

A bibliometric analysis of the Journal of Molecular Graphics and Modelling: An update.

This paper provides a bibliometric review of the articles published in the Journal of Molecular Graphics and Modelling (formerly the Journal of Molecular Graphics). The journal has grown rapidly since its establishment in 1983, with articles coming from countries throughout the world. It now primarily contains articles describing applications of molecular graphics and modelling in chemical and biological systems, rather than the underlying technology that was the focus of many of the early papers in the journal; however, it is these early, system-based papers that continue to attract by far the largest numbers of citations.

Novel base triples in RNA structures revealed by graph theoretical searching methods.

BACKGROUND: Highly hydrogen bonded base interactions play a major part in stabilizing the tertiary structures of complex RNA molecules, such as transfer-RNAs, ribozymes and ribosomal RNAs. RESULTS: We describe the graph theoretical identification and searching of highly hydrogen bonded base triples, where each base is involved in at least two hydrogen bonds with the other bases. Our approach correlates theoretically predicted base triples with literature-based compilations and other actual occurrences in crystal structures. The use of 'fuzzy' search tolerances has enabled us to discover a number of triple interaction types that have not been previously recorded nor predicted theoretically. CONCLUSIONS: Comparative analyses of different ribosomal RNA structures reveal several conserved base triple motifs in 50S rRNA structures, indicating an important role in structural stabilization and ultimately RNA function.

Decision support for the quickest detection of critical COVID-19 phases.

During the course of an epidemic, one of the most challenging tasks for authorities is to decide what kind of restrictive measures to introduce and when these should be enforced. In order to take informed decisions in a fully rational manner, the onset of a critical regime, characterized by an exponential growth of the contagion, must be identified as quickly as possible. Providing rigorous quantitative tools to detect such an onset represents an important contribution from the scientific community to proactively support the political decision makers. In this paper, leveraging the quickest detection theory, we propose a mathematical model of the COVID-19 pandemic evolution and develop decision tools to rapidly detect the passage from a controlled regime to a critical one. A new sequential test-referred to as MAST (mean-agnostic sequential test)-is presented, and demonstrated on publicly available COVID-19 infection data from different countries. Then, the performance of MAST is investigated for the second pandemic wave, showing an effective trade-off between average decision delay [Formula: see text] and risk [Formula: see text], where [Formula: see text] is inversely proportional to the time required to declare the need to take unnecessary restrictive measures. To quantify risk, in this paper we adopt as its proxy the average occurrence rate of false alarms, in that a false alarm risks unnecessary social and economic disruption. Ideally, the decision mechanism should react as quick as possible for a given level of risk. We find that all the countries share the same behaviour in terms of quickest detection, specifically the risk scales exponentially with the delay, [Formula: see text], where [Formula: see text] depends on the specific nation. For a reasonably small risk level, say, one possibility in ten thousand (i.e., unmotivated implementation of countermeasures every 27 years, on the average), the proposed algorithm detects the onset of the critical regime with delay between a few days to 3 weeks, much earlier than when the exponential growth becomes evident. Strictly from the quickest-detection perspective adopted in this paper, it turns out that countermeasures against the second epidemic wave have not always been taken in a timely manner. The developed tool can be used to support decisions at different geographic scales (regions, cities, local areas, etc.), levels of risk, instantiations of controlled/critical regime, and is general enough to be applied to different pandemic time-series. Additional analysis and applications of MAST are made available on a dedicated website.

COVID-19 impact on global maritime mobility.

To prevent the outbreak of the Coronavirus disease (COVID-19), many countries around the world went into lockdown and imposed unprecedented containment measures. These restrictions progressively produced changes to social behavior and global mobility patterns, evidently disrupting social and economic activities. Here, using maritime traffic data collected via a global network of Automatic Identification System (AIS) receivers, we analyze the effects that the COVID-19 pandemic and containment measures had on the shipping industry, which accounts alone for more than 80% of the world trade. We rely on multiple data-driven maritime mobility indexes to quantitatively assess ship mobility in a given unit of time. The mobility analysis here presented has a worldwide extent and is based on the computation of: Cumulative Navigated Miles (CNM) of all ships reporting their position and navigational status via AIS, number of active and idle ships, and fleet average speed. To highlight significant changes in shipping routes and operational patterns, we also compute and compare global and local vessel density maps. We compare 2020 mobility levels to those of previous years assuming that an unchanged growth rate would have been achieved, if not for COVID-19. Following the outbreak, we find an unprecedented drop in maritime mobility, across all categories of commercial shipping. With few exceptions, a generally reduced activity is observable from March to June 2020, when the most severe restrictions were in force. We quantify a variation of mobility between -5.62 and -13.77% for container ships, between +2.28 and -3.32% for dry bulk, between -0.22 and -9.27% for wet bulk, and between -19.57 and -42.77% for passenger traffic. The presented study is unprecedented for the uniqueness and completeness of the employed AIS dataset, which comprises a trillion AIS messages broadcast worldwide by 50,000 ships, a figure that closely parallels the documented size of the world merchant fleet.

Bibliometric analysis of Chinese research on cyclization, MALDI-TOF, and antibiotics.

This paper reports a bibliometric analysis of the impact of research in China on cyclization, MALDI-TOF, and antibiotics, comparing this research with that in the USA, Germany, and Japan. It is shown that the productivity of the Chinese research (in terms of numbers of publications) is growing rapidly; however, this growth has not, to date, been accompanied by an analogous growth in impact (in terms of citations to the published work). A citation analysis of national and international collaboration patterns shows that collaborative research does not invariably result in a larger number of citations; in part, at least, this is shown to be due to the dominant role played by the publications of the Chinese Academy of Sciences.

Inverse frequency weighting of fragments for similarity-based virtual screening.

This paper discusses the weighting of two-dimensional fingerprints for similarity-based virtual screening, specifically the use of weights that assign greatest importance to the substructural fragments that occur least frequently in the database that is being screened. Virtual screening experiments using the MDL Drug Data Report and World of Molecular Bioactivity databases show that the use of such inverse frequency weighting schemes can result, in some circumstances, in marked increases in screening effectiveness when compared with the use of conventional, unweighted fingerprints. Analysis of the characteristics of the various schemes demonstrates that such weights are best used to weight the fingerprint of the reference structure in a similarity search, with the database structures' fingerprints unweighted. However, the increases in performance resulting from such weights are only observed with structurally homogeneous sets of active molecules; when the actives are diverse, the best results are obtained using conventional, unweighted fingerprints for both the reference structure and the database structures.

Ligand-based virtual screening using Bayesian networks.

A Bayesian inference network (BIN) provides an interesting alternative to existing tools for similarity-based virtual screening. The BIN is particularly effective when the active molecules being sought have a high degree of structural homogeneity but has been found to perform less well with structurally heterogeneous sets of actives. In this paper, we introduce an alternative network model, called a Bayesian belief network (BBN), that seeks to overcome this limitation of the BIN approach. Simulated virtual screening experiments with the MDDR, WOMBAT and MUV data sets show that the BIN and BBN methods allow effective screening searches to be carried out. However, the results obtained are not obviously superior to those obtained using a much simpler approach that is based on the use of the Tanimoto coefficient and of the square roots of fragment occurrence frequencies.