The LOTUS initiative for open knowledge management in natural products research

Abstract

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 for data access, both within the discipline and for integration and interoperability between related fields. 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 750,000+ referenced structure-organism pairs. LOTUS data is hosted on Wikidata and regularly mirrored on https://lotus.naturalproducts.net. Data sharing within the Wikidata framework broadens data access and interoperability, opening new possibilities for community curation and evolving publication models. Furthermore, embedding LOTUS data into the vast Wikidata knowledge graph will facilitate new biological and chemical insights. The LOTUS initiative represents an important advancement in the design and deployment of a comprehensive and collaborative natural products knowledge base.

Keywords: LOTUS Initiative; Wikidata; computational biology; ecology; knowledge graph; linked data; natural products; open science; systems biology.

Figure 1.. Blueprint of the LOTUS initiative.

Data undergo a four-stage process: (1) Harmonization, (2) Processing, (3) Validation, and (4) Dissemination. The process was designed to incorporate future contributions (5), either by the addition of new data from within Wikidata (a) or new sources (b) or via curation of existing data (c). The figure is available under the CC0 license at https://commons.wikimedia.org/wiki/File:Lotus_initiative_1_blueprint.svg.

Figure 2.. Alluvial plot of the data transformation flow within LOTUS during the automated curation and validation processes.

The figure also reflects the relative proportions of the data stream in terms of the contributions from the various sources (‘source’ block, left), the composition of the harmonized subcategories (‘original subcategory’ block, middle) and the validated data after curation (‘processed category’ block, right). Automatically validated entries are represented in green, rejected entries in blue. The figure is available under the CC0 license at https://commons.wikimedia.org/wiki/File:Lotus_initiative_1_alluvial_plot.svg.

Figure 3.. Illustration of the ‘found in taxon’ statement section on the Wikidata page of erysodine Q27265641 showing a selection of erysodine-containing taxa and the references documenting these occurrences.

Figure 4.. Distribution of ‘structures per organism’ and ‘organisms per structure’.

The number of organisms linked to the planar structure of β-sitosterol (KZJWDPNRJALLNS) and the number of chemical structures in Arabidopsis thaliana are two exemplary highlights. A. thaliana contains 687 different short InChIKeys (i.e. 2D structures) and KZJWDPNRJALLNS is reported in 3979 distinct organisms. Less than 10% of the species contain more than 80% of the structural diversity present within LOTUS. In parallel, 80% of the species present in LOTUS are linked to less than 10% of the structures. The figure is available under the CC0 license at https://commons.wikimedia.org/wiki/File:Lotus_initiative_1_structure_organism_distribution.svg.

Figure 5.. UpSet plots of the individual contribution of electronic NP resources to the planar structures found in Arabidopsis thaliana (A) and to organisms reported to contain the planar structure of β-sitosterol (KZJWDPNRJALLNS) (B).

UpSet plots are evolved Venn diagrams, allowing to represent intersections between multiple sets. The horizontal bars on the lower left represent the number of corresponding entries per electronic NP resource. The dots and their connecting line represent the intersection between source and consolidate sets. The vertical bars indicate the number of entries at the intersection. For example, 479 organisms containing the planar structure of β-sitosterol are present in both UNPD and NAPRALERT, whereas each of them respectively reports 1349 and 2330 organisms containing the planar structure of β-sitosterol. The figure is available under the CC0 license at https://commons.wikimedia.org/wiki/File:Lotus_initiative_1_upset_plot.svg.

Figure 6.. TMAP visualizations of the chemical diversity present in LOTUS.

Each dot corresponds to a chemical structure. A highly specific quassinoid (NXZXPYYKGQCDRO) (light green star) and an ubiquitous stigmastane steroid (KZJWDPNRJALLNS) (dark green diamond) are mapped as examples in all visualizations. In panel A., compounds (dots) are colored according to the NPClassifier chemical class they belong to. In panel B., compounds that are mostly reported in the Simaroubaceae family are highlighted in blue. Finally, in panel C., the compounds are colored according to the specificity score of chemical classes found in biological organisms. This biological specificity score at a given taxonomic level for a given chemical class is calculated as a Jensen-Shannon divergence. A score of 1 suggests that compounds are highly specific, 0 that they are ubiquitous. Zooms on a group of compounds of high biological specificity score (in pink) and on compounds of low specificity (blue) are depicted. An interactive HTML visualization of the LOTUS TMAP is available at https://lotus.nprod.net/post/lotus-tmap/ and archived at https://doi.org/10.5281/zenodo.5801807 (Rutz and Gaudry, 2021). The figure is available under the CC0 license at https://commons.wikimedia.org/wiki/File:Lotus_initiative_1_biologically_interpreted_chemical_tree.svg.

Figure 7.. LOTUS provides new means of exploring and representing chemical and biological diversity.

The tree generated from current LOTUS data builds on biological taxonomy and employs the kingdom as tips label color (only families containing 50+ chemical structures were considered). The outer bars correspond to the most specific chemical class found in the biological family. The height of the bar is proportional to a specificity score corresponding to a Jaccard index between the chemical class and the biological family. The bar color corresponds to the chemical pathway of the most specific chemical class in the NPClassifier classification system. The size of the leaf nodes corresponds to the number of genera reported in the family. The figure is vectorized and zoomable for detailed inspection and is available under the CC0 license at https://commons.wikimedia.org/wiki/File:Lotus_initiative_1_chemically_interpreted_biological_tree.svg.

Figure 7—figure supplement 1.. Distribution of β-sitosterol and related chemical parents among families with at least 50 reported compounds present in LOTUS.

Script used for the generation of each tree in the figure is the same (src/4_visualizing/plot_magicTree.R) as for Figure 7 as both figures are related. The figure is available under CC0 license at https://commons.wikimedia.org/wiki/File:Lotus_initiative_1_chemically_interpreted_biological_tree_supplement.svg.

Author response image 1.. Left heuristic vs right Overlap index.