Biology subjects

Krejci, A.

Publications and source records attributed to Krejci, A..

4 recordsLinked to original sources

bioRxiv2026

Reduced body size of Varroa destructor associated with varroa-resistant honey bee colonies across Europe

The ectoparasitic mite Varroa destructor is the most significant parasite of the Western honey bee (Apis mellifera) and a major driver of colony losses worldwide. Although extensive research has focused on behavioral and physiological mechanisms of host resistance, comparatively little attention has been paid to potential phenotypic responses of the parasite itself. Here we investigated body size variation in Varroa destructor associated with varroa-resistant and non-resistant honey bee colonies across four European countries. We quantified the dorsal shield area of adult female mites from multiple colonies differing in the honey bee colonies resistance status, using standardized digital image analysis. Across geographically distant non-resistant populations, mite body size was remarkably consistent, with a median dorsal shield area of 1.47 mm2. In contrast, mites originating from varroa-resistant colonies were consistently smaller, with a median dorsal shield area of 1.37 mm2, representing an approximately 6.8% reduction in body size. This pattern was reproducible across different geographical areas, honey bee genetic backgrounds and beekeeping practices. The striking stability of mite body size in non-resistant populations contrasted with the consistent reduction observed in mites associated with resistant hosts, suggesting a host associated shift in parasite phenotype. Because body size in arthropods integrates developmental conditions, nutritional availability and resource allocation, the observed pattern may reflect altered developmental environments and selective pressures imposed by resistant hosts. Our results show a consistent morphological shift in this globally important parasite associated with resistant hosts and suggest that dorsal shield size in Varroa could serve as a new selection marker for varroa-resistant honey bee colonies.

evolutionary biology↗

bioRxiv2023

Decoding Heterogenous Single-cell Perturbation Responses

Understanding diverse responses of individual cells to the same perturbation is central to many biological and biomedical problems. Current methods, however, do not precisely quantify the strength of perturbation responses and, more importantly, reveal new biological insights from heterogeneity in responses. Here we introduce the perturbation-response score (PS), based on constrained quadratic optimization, to quantify diverse perturbation responses at a single-cell level. Applied to single-cell transcriptomes of large-scale genetic perturbation datasets (e.g., Perturb-seq), PS outperforms existing methods for quantifying partial gene perturbation responses. In addition, PS presents two major advances. First, PS enables large-scale, single-cell-resolution dosage analysis of perturbation, without the need to titrate perturbation strength. By analyzing the dose-response patterns of over 2,000 essential genes in Perturb-seq, we identify two distinct patterns, depending on whether a moderate reduction in their expression induces strong downstream expression alterations. Second, PS identifies intrinsic and extrinsic biological determinants of perturbation responses. We demonstrate the application of PS in contexts such as T cell stimulation, latent HIV-1 expression, and pancreatic cell differentiation. Notably, PS unveiled a previously unrecognized, cell-type-specific role of coiled-coil domain containing 6 (CCDC6) in guiding liver and pancreatic lineage decisions, where CCDC6 knockouts drive the endoderm cell differentiation towards liver lineage, rather than pancreatic lineage. The PS approach provides an innovative method for dose-to-function analysis and will enable new biological discoveries from single-cell perturbation datasets. One sentence summaryWe present a method to quantify diverse perturbation responses and discover novel biological insights in single-cell perturbation datasets.

bioinformatics↗

bioRxiv2023

Mapping the functional impact of non-coding regulatory elements in primary T cells through single-cell CRISPR screens

Drug targets with human genetic evidence are expected to increase clinical success by at least two-fold. Yet, translating disease-associated genetic variants into functional knowledge remains a fundamental challenge of early drug discovery. A key issue is that, currently, the vast majority of complex disease associations cannot be cleanly mapped to a gene. Immune disease-associated variants are enriched within regulatory elements, such as distal enhancers, found in T cell-specific open chromatin regions. To identify the genes and thus the molecular programs modulated by these regulatory elements, we developed a CRISPRi-based single-cell functional screening approach in primary human CD4+ T cells. Our pipeline enables the interrogation of transcriptomic changes induced by the perturbation of regulatory elements at scale. We first optimised a highly efficient CRISPRi protocol in primary human CD4+ T cells via CROPseq vectors. Subsequently, we performed a proof-of-concept screen targeting 45 non-coding regulatory elements and 35 transcription start sites and profiled approximately 250,000 CD4+ T cell single-cell transcriptomes. We developed a bespoke analytical pipeline for element-to-gene (E2G) mapping and demonstrate that our method can identify both previously annotated and novel E2G links. Lastly, we integrated genetic association data for immune-related traits and demonstrate how our platform can aid in the identification of effector genes for GWAS loci.

genomics↗

bioRxiv2016

GLASS: assisted and standardized assessment of gene variations from Sanger sequence trace data

MotivationSanger sequencing remains the reference method for sequence variant detection, especially in a clinical setting. However, chromatogram interpretation often requires manual inspection and in some cases considerable expertise. Additionally, variant reporting and nomenclature is typically left to the user, which can lead to inconsistencies.\n\nResultsWe introduce GLASS, a tool built to assist with the assessment of gene variations in Sanger sequencing data. Critically, it provides a standardized variant output as recommended by the Human Genome Variation Society.\n\nAvailabilityThe program is freely available online at http://bat.infspire.org/genomepd/glass/.\n\nContactnikos.darzentas@gmail.com, malcikova.jitka@fnbrno.cz\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗