Dragon exploration system on marine sponge compounds interactions
© Sagar et al.; licensee Chemistry Central Ltd. 2013
Received: 6 October 2012
Accepted: 14 February 2013
Published: 16 February 2013
Natural products are considered a rich source of new chemical structures that may lead to the therapeutic agents in all major disease areas. About 50% of the drugs introduced in the market in the last 20 years were natural products/derivatives or natural products mimics, which clearly shows the influence of natural products in drug discovery.
In an effort to further support the research in this field, we have developed an integrative knowledge base on Marine Sponge Compounds Interactions (Dragon Exploration System on Marine Sponge Compounds Interactions - DESMSCI) as a web resource. This knowledge base provides information about the associations of the sponge compounds with different biological concepts such as human genes or proteins, diseases, as well as pathways, based on the literature information available in PubMed and information deposited in several other databases. As such, DESMSCI is aimed as a research support resource for problems on the utilization of marine sponge compounds. DESMSCI allows visualization of relationships between different chemical compounds and biological concepts through textual and tabular views, graphs and relational networks. In addition, DESMSCI has built in hypotheses discovery module that generates potentially new/interesting associations among different biomedical concepts. We also present a case study derived from the hypotheses generated by DESMSCI which provides a possible novel mode of action for variolins in Alzheimer’s disease.
DESMSCI is the first publicly available (http://www.cbrc.kaust.edu.sa/desmsci) comprehensive resource where users can explore information, compiled by text- and data-mining approaches, on biological and chemical data related to sponge compounds.
KeywordsSponge compounds interactions Natural products Text-mining Information integration Knowledge base
Natural products are chemical compounds that originate from living organisms and play a major role in the drug discovery and development process. The importance of natural products in drug discovery has been discussed in several reviews and reports [1–5]. About 200,000 natural compounds are currently known . The chemical diversity of natural compounds, especially the diversity of scaffolds and the large number of chiral centers represent a basis for their use in drug therapy. About 50% of the drugs introduced in the market during the last 20 years are derived directly or indirectly from natural products . A total of 1,184 new approved drugs have been identified covering all diseases/countries/sources in the years 01/1981-06/2006. Out of these, only 30% were synthetic in origin, which demonstrates the influence of natural products/derivatives/natural product mimics on drug discovery process .
The marine organisms adapted to unusual conditions of higher salt content, low or zero light, unusually low or high temperature and pressure, have offered a number of lead bioactive molecules with unique novel structures and distinct biological activities. Marine sponges have been considered a valuable source of bioactive molecules with different pharmacological activities. Sponges produce a wide array of secondary metabolites ranging from derivatives of amino acids and nucleosides to porphyrins, terpenoids macrolids, sterols, and others. Reports of isolation and identification of natural products from marine sponges are being published since early 1950’s. The isolation and identification of spongothymidine and spongouridine from the Caribbean sponge Tethya crypta[9–11], led to the discovery of close analogues, cytosine arabinoside or Ara-C, as a potent antileukemic agent and adenine arabinoside or Ara-A, an antiviral compound, as commercial drugs. The sponge-derived apoptosis-inducing lead compounds that have potential use in cancer treatment have been described in a recent review .
Sponge derived bioactive molecules in clinical and preclinical trials
Phase III 
HTI-285 (hemiasterlin derivative)
External databases used for data integration
Number of records
Chemical Entities of Biological Interest (ChEBI)
Functional association data/networks (GeneMania)
HUGO Gene Nomenclature
Human Major Histocompatibility Complex
Immunoglobulins and T cell receptors nucleotide sequences
Oxford Human Mouse grid
Uniprot: UniProtKB/Swiss-Prot, UniProtKB/TrEMBL
Dictionaries used for text mining during creation of MSCI
Number of terms
Number of terms found
Human genes and proteins
Mode of action
Total: 5 dictionaries
DESMSCI database was built on 31 December, 2012, with a document collection consisting of 16,023 abstracts downloaded from PubMed using “porifera OR sponge OR sponges” as a query. Annotation terms we used (Table 3) were from the following dictionaries: “Sponge compounds”, “Human genes and proteins”, “Mode of action”, “Pathways”, and “Disease concepts”. The dictionary of “Sponge compounds” contains manually curated 3,050 sponge compounds (including synonyms), compiled from the published literature. The dictionary of genes and proteins contains 269,908 variants of entities covering the names, symbols, aliases, previous names and previously used symbols of human genes and proteins. The DES engine performed annotation and created indexes of terms, terms pairs and clustering of PubMed articles. Finally, DESMSCI web interface was built by using DES customizable modules. Data integration to local MRS installation was implemented by using SOAP based MRS client [http://search.cpan.org/dist/MRS-Client/].
The details about the methods applied by DES, how to use the knowledge base and other relevant details are provided in the documentation (http://www.cbrc.kaust.edu.sa/desmsci/desmsci.pdf). The accuracy of the integrated data was evaluated earlier in Sagar et al.  in terms of precision (ability to identify the correct entities of a specific type in PubMed abstracts relative to all identified entities of that type) and recall (the ability to identify correct entities of a specific types present in the abstracts relative to all entities of that type present in the abstracts) and were found to be in the range of 81%–100% for different categories, with an average F-measure of 92.9%. In another report from our group, precison and recall were in ranged from 78%–99% and 87%–100% . A brief comparison with PolySearch , a web based text-mining system, has also been reported . However, these accuracy assessments can only be used as a guide and not as a claim of absolute accuracy of the system.
Generation of text-mined and data-mined reports
Hypothesis generation is one of the most useful features in DESMSCI. It allows users to infer potentially new/interesting relationships among different concepts. The module is based on Swanson’s ABC model . It would be very difficult if not impossible to manually extract the associations between the concepts (which do not appear in the same document), to infer potentially new hypotheses, especially with the large amount of available concepts and literature. DESMSCI allows for the inspection of automatically generated hypotheses and their validity by retrieving the PubMed document(s) related to the concepts linked through the hypothesis. The initial hint that the association between the two concepts may be a candidate for a hypothesis appears in the case when there is no connection (co-occurrence in the same PubMed entry) of the concepts found in the analyzed set of PubMed entries. DESMSCI provides for the further inspection if the same two concepts co-occur in the same PubMed entry by querying the whole PubMed (22,000,000+ entries). If no PubMed document containing both of the terms is found, it suggests a possible new association between such concepts, a hypothesis for further exploration.
Variolins for preventing neurodegeneration in Alzheimer’s disease
Variolins are anti-tumor marine alkaloids isolated from a rare Antarctic sponge Kirkpatrickia Varialosa in 1994 . Variolin-B (VAR-B) was most cytotoxic among the four compounds isolated from sponge and later derivatives of variolins were synthesized to enhance aqueous stability as well as their anti-cancer activities . The studies on a derivative (dVAR-B) of VAR-B showed that variolins are CDK (cyclin-dependent kinases) inhibitors and induce apoptosis via p53 independent mechanism . Cyclins, CDKs and cyclin-dependent kinase inhibitors (CKIs) are cell cycle regulatory proteins that control cell cycle transition from one phase to another (G1, S and G2). Cyclins and CDKs form heterodimers leading to progression or inhibition of cell cycle and these pairs are further inhibited or inactivated by small CKI peptides. The cell cycle deregulation leads to neurogeneration. In neurons, cell cycle normally does not progress beyond G1 phase checkpoint, but in AD, cell cycle progresses to G2 phase that leads the cell to death , and also drives the formation of neurofibrillary tangles and amyloid plaques [27–29]. This leads to neurodegeneration which is a characteristic phenotype linked to AD . CDKs (CDK1, CDK2, and CDK5) have been associated with tau hyperphosphorylation, amyloid precursor protein processing, and apoptosis due to the cell cycle deregulation in AD . Therefore, the agents that block cyclins or CDKs may further block neurodegeneration in AD patients . Thus, we can propose a hypothesis that variolins, being inhibitors of CDKs, could block neurodegeneration in AD. Consequently, this potential activity of variolins could be tested for its effects in AD.
Furospongolide as an angiogenesis blocker
DESMSCI is the first publicly available knowledge base where users can explore various types of information about sponge natural products at chemical, biological and molecular levels. Hypothesis generation is an important component of this system and it can help researchers to develop new ideas and test them by using the available literature and other information repositories. We hope that this knowledge base will serve as a useful complement to the existing public resources and for researchers involved in natural products’ research at any level across different disciplines.
DESMSCI will be updated every six months and the information from all new studies published in that period will be incorporated. As the number of concepts grows with new incoming literature, the dictionaries will also be further curated and expanded. The improvement in the quality of dictionaries will certainly enhance the accuracy of the knowledge base. The comments obtained from the users will also help to improve the functionality of DESMSCI.
Dragon Exploration System
Dragon Exploration System on Marine Sponge Compounds Interactions
Cyclin-dependent kinase inhibitors
Vascular endothelial growth factor
Hypoxia inducing factor
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