Biology subjects

Balke, J.

Publications and source records attributed to Balke, J..

3 recordsLinked to original sources

bioRxiv2026

Increased variability and reduced phenotypic robustness in clonal Drosophila mercatorum

Quantitative genetics predicts that reducing genetic variability should reduce phenotypic variability, a common principle that underlies the widespread use of inbred, isogenic, and clonal animals in biomedical research. Yet extreme homozygosity can also expose recessive deleterious alleles and detoriate developmental buffering, potentially destabilizing rather than canalizing phenotypic outcomes. We tested this conflict directly in Drosophila mercatorum, a facultatively parthenogenic fly species in which pronuclear duplication results in fully homozygous, clonal offspring already after a single generation. Contrary to the expectation that genetic uniformity should reduce phenotypic variability, clonal parthenogenic flies showed changes in trait means, trait-dependent changes in interindividual variation, increased fluctuating asymmetry, and, most consistently, reduced behavioral and developmental canalization across a broad set of parameters. These effects on phenotypes spanned visually guided locomotion, circadian activity, wing morphology, bristle patterning, eye anatomy, brain volume, and serotonergic neuron numbers and were associated with reduced survival under environmental stress. Inbreeding of sexual D. mercatorum reproduced several of these phenotypic changes, whereas a single generation of outcrossing restored phenotypic robustness and the resulting F1 hybrids even exceeded the wild-type controls in several traits, consistent with a hybrid vigor effect. Together, these experiments identify loss of heterozygosity, rather than clonality per se, as the primary driver of developmental instability. Our findings show that genetic uniformity achieved through homozygosity can amplify stochastic phenotypic divergence by weakening developmental canalization, and suggest that the genetic context in which experimental standardization is achieved, especially heterozygosity, matters as much as the degree of genetic uniformity itself.

genetics↗

bioRxiv2025

FUSED: CROSS-DOMAIN INTEGRATION OF FOUNDATION MODELS FOR CANCER DRUG RESPONSE PREDICTION

AO_SCPLOWBSTRACTC_SCPLOWAI-driven methods for predicting drug responses hold promise for advancing personalized cancer therapy, but cancer heterogeneity and the high cost of data generation pose substantial challenges. Here we explore the transfer learning capability and introduce FUSED (Fusion of Foundation Model Embeddings for Drug Response Prediction), a novel architecture for cross-domain foundation model (FM) integration. By systematically benchmark FMs across two domains - molecular FM for drugs and single-cell FM for cell lines, we demonstrate that integrating single-cell FMs substantially reduces the number of input features required for cell line representation. Among FMs, Molformer significantly outperforms ChemBERTa, and scGPT surpasses scFoundation in predictive accuracy and training stability. Moreover, integrating single-cell FMs improves performance in both drug-known and leave-one-drug-out scenarios. These findings highlight the potential of cross-domain FM integration for more efficient and robust drug response prediction.

bioinformatics↗

bioRxiv2019

Modality-specific circuits for skylight orientation in the fly visual system

In the fly optic lobe [~]800 highly stereotypical columnar microcircuits are arranged retinotopically to process visual information. Differences in cellular composition and synaptic connectivity within functionally specialized columns remains largely unknown. Here we describe the cellular and synaptic architecture in medulla columns located downstream of photoreceptors in the dorsal rim area (DRA), where linearly polarized skylight is detected for guiding orientation responses. We show that only in DRA medulla columns, both R7 and R8 photoreceptors target to the bona fide R7 target layer where they form connections with previously uncharacterized, modality-specific Dm neurons: Two morphologically distinct DRA-specific cell types (termed Dm-DRA1 and Dm-DRA2) stratify in separate sublayers and exclusively contact polarization-sensitive DRA inputs, while avoiding overlaps with color-sensitive Dm8 cells. Using the activity-dependent GRASP and trans-Tango techniques, we confirm that DRA R7 cells are synaptically connected to Dm-DRA1, whereas DRA R8 form synapses with Dm-DRA2. Finally, using live imaging of ingrowing pupal photoreceptor axons, we show that DRA R7 and R8 termini reach layer M6 sequentially, thus separating the establishment of different synaptic connectivity in time. We propose that a duplication of R7[->]Dm circuitry in DRA ommatidia serves as an ideal adaptation for detecting linearly polarized skylight using orthogonal e-vector analyzers.

neuroscience↗