RESULTS: Twenty two of the top-ranked water-soluble compounds were selected for inhibitory screening against PAD4. Three compounds showed significant inhibition of PAD4 and their IC50 values were investigated. The structures of the three compounds show no resemblance with previously discovered PAD4 inhibitors, nor with existing drugs for RA treatment.
CONCLUSION: Three compounds were discovered as potential inhibitors of PAD4 by virtual screening. The compounds are commercially available and can be used as scaffolds to design more potent inhibitors against PAD4.
RESULTS: Using three simple heuristics, we designed RNA sensors that can mimic the function of a seven-segment display (SSD). Ten independent and orthogonal sensors representing the numerals 0 to 9 are designed and constructed. Each sensor has its own unique oligonucleotide binding site region that is activated uniquely by a specific input. Each operator was subjected to a stringent in silico filtering. Random sensors were selected and functionally validated via ribozyme self cleavage assays that were visualized via electrophoresis.
CONCLUSIONS: By utilising simple permutation and randomisation in the sequence design phase, we have developed functional RNA sensors thus demonstrating that even the simplest of computational methods can greatly aid the design phase for constructing functional molecular devices.
RESULTS: A first set of sORFs was identified from existing annotations that fitted the maximum of 80 residues criterion. A second set was predicted using parameters that specifically searched for ORF candidates of 80 codons or less in the exonic, intronic and intergenic sequences of the subject genomes. A total of 1986 conserved sORFs were predicted and characterized.
CONCLUSIONS: It is evident that numerous open reading frames that could potentially encode for polypeptides consisting of 80 amino acid residues or less are overlooked during standard gene prediction and annotation. From our results, additional targeted reannotation of genomes is clearly able to complement standard genome annotation to identify sORFs. Due to the lack of, and limitations with experimental validation, we propose that a simple conservation analysis can provide an acceptable means of ensuring that the predicted sORFs are sufficiently clear of gene prediction artefacts.
RESULTS: Here, we present the CircPrime web-based platform, providing a user-friendly solution for DNA primer design and thermocycling conditions for circRNA identification with routine PCR methods.
CONCLUSIONS: User-friendly CircPrime web platform ( http://circprime.elgene.net/ ) works with outputs of the most popular bioinformatic predictors of circRNAs to design specific circular RNA primers. CircPrime works with circRNA coordinates and any reference genome from the National Center for Biotechnology Information database).
RESULTS: Here, we analyzed genetic data of 230 B. flabellifer accessions across Thailand using 17 EST-SSR and 12 gSSR polymorphic markers. Clustering analysis revealed that the population consisted of two genetic clusters (STRUCTURE K = 2). Cluster I is found mainly in southern Thailand, while Cluster II is found mainly in the northeastern. Those found in the central are of an extensive mix between the two. These two clusters are in moderate differentiation (F ST = 0.066 and N M = 3.532) and have low genetic diversity (HO = 0.371 and 0.416; AR = 2.99 and 3.19, for the cluster I and II respectively). The minimum numbers of founders for each genetic group varies from 3 to 4 individuals, based on simulation using different allele frequency assumptions. These numbers coincide with that B. flabellifer is dioecious, and a number of seeds had to be simultaneously introduced for obtaining both male and female founders.
CONCLUSIONS: From these data and geographical and historical evidence, we hypothesize that there were at least two different invasive events of B. flabellifer in Thailand. B. flabellifer was likely brought through the Straits of Malacca to be propagated in the southern Thailand as one of the invasive events before spreading to the central Thailand. The second event likely occurred in Khmer Empire, currently Cambodia, before spreading to the northeastern Thailand.
RESULTS: We propose a succinct representation of the distance matrices which tremendously reduces the space requirement. We give a complete solution, called SuperRec, for the inference of chromosomal structures from Hi-C data, through iterative solving the large-scale weighted multidimensional scaling problem.
CONCLUSIONS: SuperRec runs faster than earlier systems without compromising on result accuracy. The SuperRec package can be obtained from http://www.cs.cityu.edu.hk/~shuaicli/SuperRec .
RESULTS: We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC50) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC50 of 0.8-1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control.
CONCLUSIONS: DeSigN is a robust method that is useful for the identification of candidate drugs using an input gene signature obtained from gene expression analysis. This user-friendly platform could be used to identify drugs with unanticipated efficacy against cancer cell lines of interest, and therefore could be used for the repurposing of drugs, thus improving the efficiency of drug development.
RESULTS: We re-sequenced the H. gammarus mitogenome on an Oxford Nanopore Minion flowcell and performed a long-read only assembly, generating a complete mitogenome assembly for H. gammarus. In contrast to previous reporting, we found an intact mitochondrial nad2 gene in the H. gammarus mitogenome and showed that its gene organization is broadly similar to that of the American lobster (H. americanus) except for the presence of a large tandemly duplicated region with evidence of pseudogenization in one of each duplicated protein-coding genes.
CONCLUSIONS: Using the European lobster as an example, we demonstrate the value of Oxford Nanopore long read technology in resolving problematic mitogenome assemblies. The increasing accessibility of Oxford Nanopore technology will make it an attractive and useful tool for evolutionary biologists to verify new and existing unusual mitochondrial gene rearrangements recovered using first and second generation sequencing technologies, particularly those used to make phylogenetic inferences of evolutionary scenarios.
METHODS: To answer this demand, the Health Equity Assessment Toolkit (HEAT), was developed between 2014 and 2016. The software, which contains the World Health Organization's Health Equity Monitor database, allows the assessment of inequalities within a country using over 30 reproductive, maternal, newborn and child health indicators and five dimensions of inequality (economic status, education, place of residence, subnational region and child's sex, where applicable).
RESULTS/CONCLUSION: HEAT was beta-tested in 2015 as part of ongoing capacity building workshops on health inequality monitoring. This is the first and only application of its kind; further developments are proposed to introduce an upload data feature, translate it into different languages and increase interactivity of the software. This article will present the main features and functionalities of HEAT and discuss its relevance and use for health inequality monitoring.