Biology subjects

Nesmelov, A.

Publications and source records attributed to Nesmelov, A..

4 recordsLinked to original sources

bioRxiv2026

Benchmarking of bulk transcriptomic harmonization tools in a multi-platform B-cell lymphoma cohort identifies feature-specific quantile normalization and surrogate variable analysis as top-performing methods

Cross-platform harmonization of bulk transcriptomic datasets remains a fundamental challenge for developing cancer biomarkers because of persistent unresolved batch effects. Most harmonization tools are benchmarked on datasets with large inter-group biological differences (for example TCGA tumor types), whereas actionable biomarker mining requires preserving subtle transcriptional distinctions between closely related diagnoses. Here we present ComboBatch, a benchmarking pipeline that evaluates the full cross-product of 14 batch-removal strategies, 3 imputation methods, 33 harmonization algorithms and 2 post-removal conditions across 7,174 samples from 88 germinal-center B-cell lymphoma cohorts spanning four transcriptomic platforms. Scoring 87 quality metrics across 2,234 harmonization approaches, we show that method choice (R2 0.36) and batch-removal strategy (0.26) are the principal determinants of harmonization quality, whereas imputation (0.016) and post-removal (<0.01) are secondary. Feature Specific Quantile Normalization and Surrogate Variable Analysis were the top methods, jointly resolving follicular lymphoma, diffuse large B-cell lymphoma and normal germinal-center B-cell differences in multi-platform and RNA-seq-only compositions, respectively. We provide a data-driven five-scenario decision tree for harmonization method selection, applicable to any retrospective multi-platform transcriptomic study. The ComboBatch pipeline is available on GitHub and can be used for harmonization, allowing bioinformaticians to utilize 33 harmonization and 3 imputation methods according to their needs.

cancer biology↗

bioRxiv2019

Intracellular localization and gene expression analysis provide new insights on LEA proteins diversity in anhydrobiotic midge

Anhydrobiosis, an adaptive ability to withstand complete desiccation, is in insects limited to a single species: the nonbiting midge Polypedilum vanderplanki (the sleeping chironomid). Evolution of anhydrobiosis in a single representative of a large genus is associated with drastic changes in genome structure, including the emergence of new multimember gene families directly involved in desiccation tolerance. Among them, Late Embryogenesis Abundant (LEA) proteins, which protect other proteins from aggregation caused by desiccation, are believed to originate via horizontal gene transfer from a bacterial donor. To obtain new insights on the biological background of the expanded 27-member LEA protein group in P. vanderplanki, we investigated the expression of corresponding genes in a P. vanderplanki-derived cell line, capable of anhydrobiosis, in a normal state and during induction of desiccation tolerance. We found that all LEA proteins genes identified in P. vanderplankis genome except PvLea16 and PvLea17 are also expressed in Pv11 cells. Their expression was elevated in response to anhydrobiosis-inducing trehalose treatment. Expression patterns of PvLea genes were well preserved in Pv11 cells in comparison to P. vanderplankis larvae both in the control group and during the anhydrobiosis cycle. We also investigated localization of LEA proteins in Pv11 cells and Sf9 cells and found a different level of conservation in intracellular localization of the protein expressed in mammalian and insect cells.

molecular biology↗

bioRxiv2018

Transcriptome analysis of Pv11 cells infers the mechanism of desiccation tolerance and recovery

The larvae of the African midge, Polypedilum vanderplanki, can enter an ametabolic state called anhydrobiosis to conquer fatal desiccation stress. The Pv11 cell line, derived from embryos of the midge, shows desiccation tolerance by pretreatment with trehalose before desiccation; they can resume proliferation after rehydration. To address the underlying molecular mechanisms, we desiccated Pv11 cells after pretreatment with the medium containing trehalose and induced proliferation by rehydration. We collected the cells at each before and after desiccation and rehydration step and performed CAGE-seq of mRNA of those cells. By analysing differentially expressed genes (DEGs) among the results of CAGE-seq, we detected 384 DEGs after trehalose treatment and 14 DEGs after rehydration. Hierarchical clustering of the identified DEGs indicated that rehydration returns their expression pattern to that in the control culture state. DEGs involved in various stress responses, detoxification of harmful chemicals, and regulation of oxidoreduction were upregulated by trehalose treatment. DEGs for rehydration supported that DNA repair is one of the potential mechanisms involves recovery. This study provided initial insight into the molecular mechanisms underlying the extreme desiccation tolerance of Pv11 cells with a potential for proliferation following rehydration.

genomics↗

bioRxiv2017

Towards Water-Free Biobanks: Long-Term Dry-Preservation At Room Temperature Of Desiccation-Sensitive Enzyme Luciferase In Air-Dried Insect Cells

Desiccation-tolerant cultured cells Pv11 derived from the anhydrobiotic Polypedilum vanderplanki embryo endure complete desiccation because of their ametabolic state and resume their metabolism after rehydration. These features led us to develop a novel dry preservation technology for enzymes as it was still unclear whether Pv11 cells preserved an exogenous enzyme in the dry state. This study shows that Pv11 cells protect an exogenous desiccation-sensitive enzyme, luciferase, preserving the enzymatic activity even after dry storage for 372 days at room temperature. A process including pre-incubation with trehalose, dehydration, storage, and rehydration allowed Pv11 (Pvll-Luc) cells stably expressing luciferase to survive desiccation and still emit luminescence caused by luciferase after rehydration. Luminescence produced by luciferase in Pvll-Luc cells after rehydration did not significantly decrease in presence of a translation inhibitor, showing that the activity did not derive from de novo enzyme synthesis following the resumption of cell metabolism. These findings indicate that the surviving Pv11 cells almost completely protect luciferase during desiccation. Lacking of the preincubation step resulted in the loss of luciferase activity after rehydration. We showed that preincubation with trehalose associated to induction of desiccation-tolerant related genes in Pv11 cells allowed effective in vivo preservation of enzymes in the dry state.

biochemistry↗