Abstract
When reading literature, we might have an emotional connection with the author, or at least what appears to be such, even when that literature is a work of fiction. But it is unclear how a ...work of fictional literature could supply the resources for such an experience. It is, after all, a work of fiction, not a report of the author’s experience, as with memoir or autobiography. The task of this paper is twofold: first, to explain the nature and value of this emotional experience; second, to argue that a fictional literary work can supply the resources for such an experience.
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.
•Three ganoderma species from the Lower Volta River Basin of Ghana were characterized.•UPLC-Q-TOF-MS-based metabolomics was applied to profile their metabolite differences.•Heatmap and PLS-DA score ...plot analyses clearly captured the metabolite differences•Overall, a total of six triterpenic acids were identified in the isolates.
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In this work, we sought to determine the differences and/or similarities in the metabolite composition of the mycelial biomass of three ganoderma isolates (Ganoderma LVRB-1, Ganoderma LVRB-9 and Ganoderma LVRB-17) from the Lower Volta River Basin of Ghana. The cultured mycelial mass of the three isolates were subjected to DNA sequencing. BLASTn searches of the internal transcribed spacer. (ITS) sequences of the isolates were conducted in the GenBank and the data obtained subjected to ITS phylogenetic analysis. Thereafter, extracts of the cultured mycelial biomass of the three isolates were subjected to untargeted ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS)-based metabolomic analysis. A cursory examination of the total ion chromatograms of the isolates gave evidence of the differential levels of the metabolites present. Further analysis of the metabolomic data using multivariate analysis better captured these marked differences in terms of the presence and/or levels of the metabolites. Finally, four lanostane triterpenoids, namely ganoderic acid C6, ganoderenic acid A, Ganoderenic acid D and ganoderic acid G, together with two annotated compounds (ganoderic acids K and AM1) were detected in the mycelia biomass of the three ganoderma isolates from the Lower Volta River Basin of Ghana. The results provide the first ever metabolomic data on the chemical constituents of the mycelial biomass of ganoderma isolates from the Lower Volta River Basin of Ghana.
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.
•Authorisation and evaluation of orphan drugs.•Similarity in the in the context of the orphan drug legislation.•2D fingerprints used to evaluate similarity of orphan medicines.•Human assessment ...versus computer assessment.
The large costs associated with modern drug discovery mean that governments and regulatory bodies need to provide economic incentives to promote the development of orphan drugs (i.e., medicinal products that are designed to treat rare disease that affect only small numbers of patients). Under European Union (EU) legislation, a medicine can only be authorised for treating a specific rare disease if it is not similar to other orphan drugs already authorised for that particular disease. Here, we discuss the use of 2D fingerprints to calculate the Tanimoto similarity between potential and existing orphan drugs for the same disease, and present logistic regression models correlating these computed similarities with the judgements of human experts.
Background
In the European Union, medicines are authorised for some rare disease only if they are judged to be dissimilar to authorised orphan drugs for that disease. This paper describes the use of ...2D fingerprints to show the extent of the relationship between computed levels of structural similarity for pairs of molecules and expert judgments of the similarities of those pairs. The resulting relationship can be used to provide input to the assessment of new active compounds for which orphan drug authorisation is being sought.
Results
143 experts provided judgments of the similarity or dissimilarity of 100 pairs of drug-like molecules from the DrugBank 3.0 database. The similarities of these pairs were also computed using BCI, Daylight, ECFC4, ECFP4, MDL and Unity 2D fingerprints. Logistic regression analyses demonstrated a strong relationship between the human and computed similarity assessments, with the resulting regression models having significant predictive power in experiments using data from submissions of orphan drug medicines to the European Medicines Agency. The BCI fingerprints performed best overall on the DrugBank dataset while the BCI, Daylight, ECFP4 and Unity fingerprints performed comparably on the European Medicines Agency dataset.
Conclusions
Measures of structural similarity based on 2D fingerprints can provide a useful source of information for the assessment of orphan drug status by regulatory authorities.
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.
It has been suggested that similarity searching using 2D fingerprints may not be suitable for scaffold hopping.
This article reports a detailed evaluation of the effectiveness of six common types of ...2D fingerprints when they are used for scaffold-hopping similarity searches of the Molecular Design Limited Drug Data Report database, World of Molecular Bioactivity database and Maximum Unbiased Validation database.
The results demonstrate that 2D fingerprints can be used for scaffold hopping, with novel scaffolds being identified in nearly every search that was carried out. The degree of enrichment depends on the structural diversity of the actives that are being sought, with the greatest enrichments often being obtained using the extended connectivity fingerprint encoding a circular substructure of diameter four bonds (ECFP4) fingerprint.
2D fingerprints provide a simple and computationally efficient way of identifying novel chemotypes in lead-discovery programs.
Background
Data fusion methods are widely used in virtual screening, and make the implicit assumption that the more often a molecule is retrieved in multiple similarity searches, the more likely it ...is to be active. This paper tests the correctness of this assumption.
Results
Sets of 25 searches using either the same reference structure and 25 different similarity measures (similarity fusion) or 25 different reference structures and the same similarity measure (group fusion) show that large numbers of unique molecules are retrieved by just a single search, but that the numbers of unique molecules decrease very rapidly as more searches are considered. This rapid decrease is accompanied by a rapid increase in the fraction of those retrieved molecules that are active. There is an approximately log-log relationship between the numbers of different molecules retrieved and the number of searches carried out, and a rationale for this power-law behaviour is provided.
Conclusions
Using multiple searches provides a simple way of increasing the precision of a similarity search, and thus provides a justification for the use of data fusion methods in virtual screening.
is a genus of biomedical fungus that is used in the development of numerous health products throughout the world. The Lower Volta River Basin of Ghana is an undulating land surface covered by ...extensive vegetation and water bodies and is rich in polypore mushrooms resembling various members of the
genus. Despite the extensive biopharmaceutical benefits of
spp., the isolates from the Lower Volta River Basin have not been properly characterized, thus limiting their use in the development of biotechnological products. In this study,
spp. collected from the Lower Volta River Basin were genetically analyzed using the nuclear ribosomal sequences, the internal transcribed spacer 2 (ITS 2), the complete internal transcribed spacer (ITS), and the nuclear large subunit (nLSU). Blastn search and sequence analysis revealed that the sample we coded as Ganoderma LVRB-2 belongs to
, whereas Ganoderma LVRB-1, Ganoderma LVRB-14, and Ganoderma LVRB-16 belong to the species
. Our analysis further demonstrates that Ganoderma LVRB-17 belongs to the species
. Thus, the five samples collected in the present study were positioned in three different distinct groups, namely
,
and
. The current data may serve as reference points for future studies.
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