Biology subjects

Tkachenko, A.

Publications and source records attributed to Tkachenko, A..

5 recordsLinked to original sources

bioRxiv2026

Correlation of OCT-Based Radiomic Signatures With Dose-Associated Radiation Response in Tumor Spheroids

BackgroundThree-dimensional tumor spheroids are an established radiobiology model, but scalable, reproducible readouts of dose-dependent radiation response are lacking. We evaluated whether optical coherence tomography (OCT) radiomics can quantify dose-associated response in spheroids, and how it compares with conventional brightfield morphology. MethodsThis in vitro, cross-sectional study used SAS oral squamous cell carcinoma spheroids seeded at two densities (5000 and 10000 cells), irradiated at 0 to 12 Gy, and imaged on days 1 to 11 post-irradiation. Each OCT acquisition yielded co-registered structural-intensity and speckle-variance volumes. Radiomic features (shape, first-order, texture) were extracted with Radiomics.jl, filtered for repeatability, correlation-pruned, and ensemble-ranked. Dose correlation was assessed by repeated 5-fold cross-validation across five regressors, comparing brightfield-only (BF), OCT-only, and combined OCT+BF feature sets with paired Wilcoxon tests. ResultsOCT-only models consistently outperformed the BF baseline (median R2 0.77 to 0.85 versus 0.61 to 0.69; p < 0.001 for all regressors). Adding brightfield to OCT gave no consistent benefit, reaching significance only for Random Forest (p = 0.026, power 0.62). A compact shared feature subset combined brightfield area dynamics with OCT texture, shape, and speckle-variance descriptors, all showing low repeat-scan variability relative to cohort variability. ConclusionsOCT radiomics provides a sensitive, reproducible, label-free high-throughput readout of spheroid radiation dose response that outperforms the current brightfield-based approach, without requiring concurrent brightfield acquisition. Key pointsO_LIOCT radiomics quantifies dose-dependent radiation response in 3D tumor spheroids. C_LIO_LIOCT-only models outperformed brightfield imaging in radiation dose prediction. C_LIO_LISelected radiomic features showed high repeatability across repeated acquisitions. C_LIO_LIAdding brightfield to OCT gave no consistent performance benefit. C_LIO_LILabel-free OCT enables reproducible, high-throughput spheroid radiation-response assessment. C_LI

cancer biology↗

bioRxiv2026

FASTR: Reimagining FASTQ via Compact Image-inspired Representation

MotivationHigh-throughput sequencing (HTS) enables population-scale genomics but generates massive datasets, creating bottlenecks in storage, transfer, and analysis. FASTQ, the standard format for over two decades, stores one byte per base and one byte per quality score, leading to inefficient I/O, high storage costs, and redundancy. Existing compression tools can mitigate some issues, but often introduce costly decompression or complex dependency issues. ResultsWe introduce FASTR, a lossless, computation-native successor to FASTQ that encodes each nucleotide together with its base quality score into a single 8-bit value. FASTR reduces file size by at least 2x while remaining fully reversible and directly usable for downstream analyses. Applying general-purpose compression tools on FASTR consistently yields higher compression ratios, 2.47, 3.64, and 4.8x faster compression, and 2.34, 1.96, 1.75x faster decompression than on FASTQ across Illumina, HiFi, and ONT reads. FASTR is machine-learning-ready, allowing reads to be consumed directly as numerical vectors or image-like representations. We provide a highly parallel software ecosystem for FASTQ-FASTR conversion and show that FASTR integrates with existing tools, such as minimap2, with minimal interface changes and no performance overhead. By eliminating decompression costs and reducing data movement, FASTR lays the foundation for scalable genomics analyses and real-time sequencing workflows. Availability and Implementationhttps://github.com/ALSER-Lab/FASTR

bioinformatics↗

bioRxiv2025

Structure-Activity Relationship Studies Towards Analogues of Pleconaril as Novel Enterovirus-D68 Capsid-Targeting Antivirals

Non-polio enteroviruses (NPEV) such as enterovirus D68 (EV-D68) that are highly infectious and associated with polio-like neurological complications have caused out-breaks, globally, in recent years. While some clinical and preclinical compounds have shown efficacy against NPEV in-vitro, liabilities that caused historical compounds such as pleconaril to fall short of FDA approval still remain. We present herein SAR and SPR studies of analogues of clinical compounds such as pleconaril and vapendavir against EV-D68 as a representative NPEV. Numerous structurally differentiated analogues with EV-D68 antiviral activity and useful ADME properties were discovered, which could serve as starting points for future EV drug discovery campaigns. Screening against a panel of enteroviruses revealed moderately broad-spectrum anti-EV activity of compound 26.

pharmacology and toxicology↗

bioRxiv2025

Discovery of orally bioavailable Zika and West Nile Virus antiviral compounds targeting the NS2B-NS3 protease

Flaviviruses are a class of pathogenic viruses with pandemic potential that are typically transmitted via infected arthropods. In addition, Zika virus is sexually transmissible and causes congenital malformations if infection occurs during pregnancy. Although over 1.5 million people were infected during the 2015-2016 Zika outbreak, to date, there are no clinical-stage vaccines or antivirals. Herein, we report the discovery of potent inhibitors of the Zika virus NS2B-NS3 protease that also show activity against the West Nile virus NS2B-NS3 protease. Starting from a crystallographic fragment screen, we employed a pharmacophore approach coupled with high-throughput library chemistry to elaborate fragments in the active site. Potent, metabolically stable, non-covalent, non-peptidomimetic inhibitors were identified with antiviral activity in vitro. The lead compound was progressed to a three-day Zika virus challenge study in AG129 mice, where it displayed significant viral RNA load reduction in both mouse plasma and spleen.

microbiology↗

bioRxiv2017

Neuronal glutamate transporters control dopaminergic signaling and compulsive behaviors

There is an ongoing debate on the contribution of the neuronal glutamate transporter EAAC1 to the onset of compulsive behaviors. Here we use behavioral, electrophysiological, molecular and viral approaches in male and female mice to identify the molecular and cellular mechanisms by which EAAC1 controls the execution of repeated motor behaviors. Our findings show that in the striatum, a brain region implicated with movement execution, EAAC1 limits group I metabotropic glutamate receptor (mGluRI) activation, facilitates D1 dopamine receptor (D1R) expression and ensures long-term synaptic plasticity. Blocking mGluRI in slices from mice lacking EAAC1 restores D1R expression and synaptic plasticity. Conversely, activation of intracellular signaling pathways coupled to mGluRI in D1R-expressing striatal neurons of mice expressing EAAC1 leads to reduced D1R expression and increased stereotyped movement execution. These findings identify new molecular mechanisms by which EAAC1 can shape glutamatergic and dopaminergic signals and control repeated movement execution.\n\nSIGNIFICANCE STATEMENTGenetic studies implicate Slc1a1, a gene encoding the neuronal glutamate transporter EAAC1, with obsessive-compulsive disorder (OCD). EAAC1 is abundantly expressed in the striatum, a brain region that is hyperactive in OCD. What remains unknown is how EAAC1 shapes synaptic function in the striatum. Our findings show that EAAC1 limits activation of metabotropic glutamate receptors (mGluRI) in the striatum and, by doing so, it promotes D1R expression. Targeted activation of signaling cascades coupled to mGluRI in mice expressing EAAC1 reduces D1R expression and triggers repeated motor behaviors in mice. These findings provide new information on the molecular basis of OCD and suggest new avenues for its treatment.

neuroscience↗