Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Optimisation of 3D intestine model & TK6 co-culture media to aid in the development of 3D micronuclei assay to assess Food nanogenotoxicity

Nanoparticles are increasingly applied in the food industry without the availability of risk assessments. To reduce animal testing in risk assessments, improvements to in vitro testing have been made over the years. Here, we aim to develop a co-culture system using 3D intestinal model and TK6 cells to study food nanogenotoxicity using cytokinesis-blocked micronucleus assay. As both cultures are grown with different media, optimisation was done to cultivate both tissue and cells in the same media to minimize changes to their native characteristics. RPMI, SMI, 10:90 and 25:75 RPMI:SMI media composition were tested on 3D tissues for 4 days and TK6 for 11 days. Using real-time PCR, both cultures had slower proliferation and were less inflamed, apoptotic and necrotic when grown in media other than their base media. For TK6, a minor and insignificant increase in the population doubling time was observed in media with SMI after 4 culture days. No changes to the basal micronuclei level in binucleated cells grown in different media compositions was seen. Furthermore, cytostasis increased throughout the culture period in all the media composition, with TK6 in SMI having the highest level of inhibition. Collectively, the results point to using SMI as the co-culture media.Bachelor of Science in Biological Science

Development of reconstructed intestinal micronucleus cytome (RICyt) assay in 3D human gut model for genotoxicity assessment of orally ingested substances

The micronucleus (MN) assay is widely used as part of a battery of tests applied to evaluate the genotoxic potential of chemicals, including new food additives and novel food ingredients. Micronucleus assays typically utilise homogenous in vitro cell lines which poorly recapitulate the physiology, biochemistry and genomic events in the gut, the site of first contact for ingested materials. Here we have adapted and validated the MN endpoint assay protocol for use with complex 3D reconstructed intestinal microtissues; we have named this new protocol the reconstructed intestine micronucleus cytome (RICyt) assay. Our data suggest the commercial 3D microtissues replicate the physiological, biochemical and genomic responses of native human small intestine to exogenous compounds. Tissues were shown to maintain log-phase proliferation throughout the period of exposure and expressed low background MN. Analysis using the RICyt assay protocol revealed the presence of diverse cell types and nuclear anomalies (cytome) in addition to MN, indicating evidence for comprehensive DNA damage and mode(s) of cell death reported by the assay. The assay correctly identified and discriminated direct-acting clastogen, aneugen and clastogen requiring exogenous metabolic activation, and a non-genotoxic chemical. We are confident that the genotoxic response in the 3D microtissues more closely resembles the native tissues due to the inherent tissue architecture, surface area, barrier effects and tissue matrix interactions. This proof-of-concept study highlights the RICyt MN cytome assay in 3D reconstructed intestinal microtissues is a promising tool for applications in predictive toxicology.Agency for Science, Technology and Research (A*STAR)National Research Foundation (NRF)Published versionThis study is supported by Industry Alignment Fund (Pre-Positioning) (IAF-PP-H18/01/a0/G14), Biomedical Research Council (BMRC, A*STAR). BPC Smith was also supported by a National Research Foundation Singapore Whitespace Grant (W20W3D0002) administered by A*STAR