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Calin, G.

Publications and source records attributed to Calin, G..

3 recordsLinked to original sources

Introducing the digital PCR data essentials standard to harmonize data structure for clinical and research use

Digital PCR (dPCR) is a powerful technology for absolute quantification of nucleic acids, valued for its accuracy, sensitivity, and repeatability. Yet, the commercialization of different instruments with proprietary software has introduced challenges to data analysis, interoperability, and comparability. Therefore, we present the Digital PCR Data Essentials Standard (DDES) - a lightweight, human- and machine-readable, and cross-platform data standard developed in collaboration with the dPCR community. The standard consists of three file types designed to enable both manual inspection and automated analysis: (i) a main file summarizing experiment and reaction-level (meta-)data; (ii) an assay file describing targets and detection chemistry, and (iii) intensity files capturing partition-level raw fluorescence data per reaction. DDES supports a wide range of current dPCR applications, including singleplex and multiplex assays, endpoint and real-time readouts, and will be curated to implement future dPCR developments. By harmonizing the data structure, DDES lays out the foundation for FAIR dPCR data practices and supports improved software compatibility, collaborative and reproducible research, and future dPCR data repositories.

bioinformatics↗

Deconvolution of Sparse-count RNA Sequencing Data for Tumor Cells Using Embedded Negative Binomial Distributions

Estimating tumor-specific transcript proportions from mixed bulk samples has potential to inform novel biology. However, estimation accuracy using existing methods in sparse-count data such as microRNA-seq and spatial transcriptomics has yet to be established. We generated a mixed small RNA benchmark dataset to demonstrate analytical challenges. To resolve them, we developed DeMixNB, a semi-reference-based deconvolution model assuming a sum of negative binomial distributions. Applications to miRNA-seq from 856 patients with breast cancer and 3,755 spatial spots from lung cancer generated either clinical or mechanistic insights into tumor cell plasticity. This supports the important utility of DeMixNB to investigate cancer RNomes.

bioinformatics↗

Drug-like small molecules that inhibit expression of the oncogenic microRNA-21

We report the discovery of a series of drug-like small molecules which bind specifically to the precursor of the oncogenic and pro-fibrotic microRNA-21 with mid-nanomolar affinity. These molecules are highly ligand-efficient (MW<330) and display specific biochemical and cellular activity by suppressing maturation of miR-21, thereby providing an avenue towards therapeutic intervention in multiple diseases where miR-21 is abnormally expressed. The small molecules target a local structure at the Dicer cleavage site and induce distinctive structural changes in the RNA which correlate with specific inhibition of miRNA processing. Structurally conservative single nucleotide substitutions eliminate the conformational change, which is not observed in other miRNA precursors. The most potent of these compounds reduces cellular proliferation and miR-21 levels in cancer cell lines without inhibiting kinases or classical receptors, while closely related compounds without this specific binding activity are inactive in cells.

biochemistry↗