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Research Insights

The Research Insights area highlights recent advances in science and medicine as well as global laboratory research. Our readers gain tremendous benefit from research discoveries in an indirect manner.

Deriving time-concordant event cascades from gene expression data: A case study for Drug-Induced Liver Injury (DILI)

Adverse event pathogenesis is often a complex process which compromises multiple events ranging from the molecular to the phenotypic level In toxicology Adverse Outcome Pathways AOPs aim to formalize this as temporal sequences of events in which event relationships should be supported by causal evidence according to the tailored BradfordHill criter...

Explainable detection of adverse drug reaction with imbalanced data distribution

Analysis of healthrelated texts can be used to detect adverse drug reactions ADR The greatest challenge for ADR detection lies in imbalanced data distributions where words related to ADR symptoms are often minority classes As a result trained models tend to converge to a point that strongly biases towards the majority class and then ignores the min...

Genome-wide cross-cancer analysis illustrates the critical role of bimodal miRNA in patient survival and drug responses to PI3K inhibitors

Heterogeneity of cancer means many tumorigenic genes are only aberrantly expressed in a subset of patients and thus follow a bimodal distribution having two modes of expression within a single population Traditional statistical techniques that compare sample means between cancer patients and healthy controls fail to detect bimodally expressed genes...

Mutational analysis of SARS-CoV-2 variants of concern reveals key tradeoffs between receptor affinity and antibody escape

SARSCoV variants with enhanced transmissibility represent a serious threat to global health Here we report machine learning models that can predict the impact of receptorbinding domain RBD mutations on receptor ACE affinity which is linked to infectivity and escape from human serum antibodies which is linked to viral neutralization

A microfluidic system that replicates pharmacokinetic (PK) profiles in vitro improves prediction of in vivo efficacy in preclinical models

Test compounds used on in vitro model systems are conventionally delivered to cell culture wells as fixed concentration bolus doses however this poorly replicates the pharmacokinetic PK concentration changes seen in vivo and reduces the predictive value of the data Herein proofofconcept experiments were performed using a novel microfluidic device

Transcriptome-wide mapping reveals a diverse dihydrouridine landscape including mRNA

Dihydrouridine is a modified nucleotide universally present in tRNAs but the complete dihydrouridine landscape is unknown in any organism We introduce dihydrouridine sequencing Dseq for transcriptomewide mapping of D with singlenucleotide resolution and use it to uncover novel classes of dihydrouridinecontaining

Comparative studies between the murine immortalized brain endothelial cell line (bEnd.3) and induced pluripotent stem cell-derived human brain endothelial cells for paracellular transport

Brain microvascular endothelial cells forming the anatomical site of the bloodbrain barrier BBB are widely used as in vitro complements to in vivo BBB studies Among the immortalized cells used as in vitro BBB models the murinederived bEnd cells offer culturing consistency and low cost and are well characterized for functional and transport assays

Designing optimal allocations for cancer screening using queuing network models

Cancer is one of the leading causes of death but mortality can be reduced by detecting tumors earlier so that treatment is initiated at a less aggressive stage The tradeoff between costs associated with screening and its benefit makes the decision of whom to screen and when a challenge To enable comparisons across screening

Integrated bioinformatics and statistical approaches to explore molecular biomarkers for breast cancer diagnosis, prognosis and therapies

Integrated bioinformatics and statistical approaches are now playing the vital role in identifying potential molecular biomarkers more accurately in presence of huge number of alternatives for disease diagnosis prognosis and therapies by reducing time and cost compared to the wetlab based experimental procedures

Generating dynamic gene expression patterns without the need for regulatory circuits

Synthetic biology has successfully advanced our ability to design and implement complex timevarying genetic circuits to control the expression of recombinant proteins However these circuits typically require the production of regulatory genes whose only purpose is to coordinate expression of other genes When designing