Complex biomedical data generated during clinical, omics and mechanism-based experiments have increasingly been exploited through cloud- and visualization-based data mining techniques. However, the scientific community still lacks an easy-to-use web service for the comprehensive visualization of biomedical data, particularly high-quality and publication-ready graphics that allow easy scaling and updatability according to user demands. Therefore, we propose a community-driven modern web service, Hiplot (https://hiplot.org), with concise and top-quality data visualization applications for the life sciences and biomedical fields. This web service permits users to conveniently and interactively complete a few specialized visualization tasks that previously could only be conducted by senior bioinformatics or biostatistics researchers. It covers most of the daily demands of biomedical researchers with its equipped 240+ biomedical data visualization functions, involving basic statistics, multi-omics, regression, clustering, dimensional reduction, meta-analysis, survival analysis, risk modelling, etc. Moreover, to improve the efficiency in use and development of plugins, we introduced some core advantages on the client-/server-side of the website, such as spreadsheet-based data importing, cross-platform command-line controller (Hctl), multi-user plumber workers, JavaScript Object Notation-based plugin system, easy data/parameters, results and errors reproduction and real-time updates mode. Meanwhile, using demo/real data sets and benchmark tests, we explored statistical parameters, cancer genomic landscapes, disease risk factors and the performance of website based on selected native plugins. The statistics of visits and user numbers could further reflect the potential impact of this web service on relevant fields. Thus, researchers devoted to life and data sciences would benefit from this emerging and free web service.

BRCA1 mutation carriers have a higher risk of developing triple-negative breast cancer (TNBC), which is a refractory disease due to its non-responsiveness to current clinical targeted therapies. Using the Sleeping Beauty transposon system in Brca1-deficient mice, we identified 169 putative cancer drivers, among which Notch1 is a top candidate for accelerating TNBC by promoting the epithelial-mesenchymal transition (EMT) and regulating the cell cycle. Activation of NOTCH1 suppresses mitotic catastrophe caused by BRCA1 deficiency by restoring S/G2 and G2/M cell cycle checkpoints, which may through activation of ATR-CHK1 signalling pathway. Consistently, analysis of human breast cancer tissue demonstrates NOTCH1 is highly expressed in TNBCs, and the activated form of NOTCH1 correlates positively with increased phosphorylation of ATR. Additionally, we demonstrate that inhibition of the NOTCH1-ATR-CHK1 cascade together with cisplatin synergistically kills TNBC by targeting the cell cycle checkpoint, DNA damage and EMT, providing a potent clinical option for this fatal disease.

Sepsis is a subtype of systemic inflammatory response syndrome (SIRS), which is characterized by infection. Circulating microRNAs (miRNAs), including miR-150, miR-146a and miR-223, are potential biomarkers of sepsis. In this study, we demonstrated that measuring the relative expression of miR-146a/U6 in plasma, using the 2−ΔΔCt method, provides a method for differentiating between sepsis and non-sepsis-SIRS. We observed a significant increase in miR-146a expression in the initial cohort of 6 non-sepsis-SIRS patients compared to the 4 sepsis patients (P=0.01) and in the second cohort of 8 non-sepsis-SIRS patients compared to the 10 sepsis patients (P=0.027). Additionally, we identified that sodium citrate and ethylenediaminetetraacetic acid (EDTA) K2 may be used as anticoagulant reagents. Generation of a standard curve is not necessary in these diagnostic tests, unless the standard of normalization is carefully selected. Thus we provide more detailed guidance for the clinical use of circulating miRNA biomarkers.

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

Whole genome duplication (WGD) results in extensive genetic redundancy. In plants and yeast, WGD is followed by rapid gene deletions and intense expression differentiation with slow functional divergence. However, the early evolution of the gene differentiation processes is poorly understood in vertebrates because almost all studied WGDs are extremely ancient, and the genomes have returned to a diploid status. Common carp had a very recent fourth round of WGD dated to 8 million years ago. It therefore constitutes an ideal model to study early-stage functional divergence and expression differentiation in vertebrates. We identified 1,757 pairs of recently duplicated genes (RDGs) originating from this specific WGD and found that most ancestral genes were retained in duplicate. Most RDGs were conserved and under selective pressure. Gene expression analysis across six tissues revealed that 92.5% of RDG pairs were co-expressed in at least one tissue and that the expression of nearly half pairs ceased to be strongly correlated, indicating slow spatial divergence but rapid expression dissociation. Functional comparison revealed that 25% of pairs had functional divergence, of which neo- and sub-functionalization were the main outcomes. Our analysis revealed slow gene loss but rapid and intense expression and function differentiation after WGD.