Biology subjects

Paoli, M.

Publications and source records attributed to Paoli, M..

7 recordsLinked to original sources

bioRxiv2025

T2T-CHM13 reference genome reduces mapping bias and enhances alignment accuracy at disease-associated variants

1The T2T-CHM13v2.0 reference genome added previously uncharacterized genomic sequences and improved the accuracy of repetitive stretches compared to former human genome assemblies. By comprehensive allelic variation analysis and read mapping statistics from sequencing reads aligned to hg38 and T2T-CHM13 assemblies in samples encompassing different sequencing designs and ethnicity groups, we observed that T2T-CHM13v2.0 assembly significantly reduces the reference mapping bias (RMB) and increases read mapping precision at clinically relevant sites, including BRCA1 pathogenic variants. Further, we report the presence of sequence dissimilarities among reference genomes in the proximity of ClinVar annotated variants, suggesting the need for data re-analysis and potential redesign of probes targeting clinically relevant regions. Overall, these findings support the implementation of T2T-CHM13 reference for the improvement of sequencing data analyses in the clinical genomic setting.

genomics↗

bioRxiv2025

Statistical Olfactory Learning in Honey Bees

Statistical learning is a key mechanism for detecting regularities in sensory inputs1,2. Among its functions is the ability to extract regularities from sequences (of sounds, objects, odors, etc.)3, enabling species to predict future events and guide behavior. This capacity has been demonstrated in vertebrates2, including human infants4, non-human primates5, and birds6. However, the minimum computational architecture required for statistical learning remains unclear. To address this issue, we studied statistical learning in the honey bee (Apis mellifera), an invertebrate model for learning studies7. We show that bees learn and recall the temporal structure of sequences of odorants, suggesting that statistical learning is a fundamental component of a conserved cognitive toolkit present even in invertebrates.

neuroscience↗

bioRxiv2024

Sensitive tumor detection, accurate quantification, and cancer subtype classification using low-pass whole methylome sequencing of plasma DNA

The analysis of circulating tumor DNA (ctDNA) is increasingly used for monitoring disease in patients with metastatic cancer. Here, we introduce a robust and reproducible strategy combining low-pass whole methylome sequencing of plasma DNA with METER, a novel computational tool. Engaging prediction models trained on independent available datasets, METER enables the detection and quantification of tumor content (TC) and performs molecular cancer subtyping. Applied to plasma methylomes from early metastatic breast cancer patients, our method demonstrated reliable quantification, sensitive tumor detection below 3% of TC, and the ability to perform accurate Estrogen Receptor (ER) subtyping. METER provided clinically relevant predictions, underscored by associations with relevant prognostic factors, robust correlation with matched circulating tumor cells, and highly correlated with patients outcomes in challenging scenarios as TC<3%. Our strategy provides comprehensive and sensitive analysis of plasma samples, serving as a valuable yet cost-effective precision oncology tool.

cancer biology↗

bioRxiv2023

Smell and Aftersmell: Fast Calcium Imaging Dynamics of Honey Bee Olfactory Coding

Odour processing exhibits multiple parallels between vertebrate and invertebrate olfactory systems. Insects, in particular, have emerged as relevant models for olfactory studies because of the tractability of their olfactory circuits. Here, we used fast calcium imaging to track the activity of projection neurons in the honey bee antennal lobe (AL) during olfactory stimulation at high temporal resolution. We observed a heterogeneity of response profiles and an abundance of inhibitory activities, resulting in various response latencies and stimulus- specific post-odour neural signatures. Recorded calcium signals were fed to a mushroom body (MB) model constructed implementing the fundamental features of connectivity between olfactory projection neurons, Kenyon cells (KC), and MB output neurons (MBON). The model accounts for the increase of odorant discrimination in the MB compared to the AL and reveals the recruitment of two distinct KC populations that represent odorants and their aftersmell as two separate but temporally coherent neural objects. Finally, we showed that the learning- induced modulation of KC-to-MBON synapses can explain both the variations in associative learning scores across different conditioning protocols used in bees and the bees response latency. Thus, it provides a simple explanation of how the time contingency between the stimulus and the reward can be encoded without the need for time tracking. This study broadens our understanding of olfactory coding and learning in honey bees. It demonstrates that a model based on simple MB connectivity rules and fed with real physiological data can explain fundamental aspects of odour processing and associative learning.

neuroscience↗

bioRxiv2022

Network plasticity in the honey bee antennal lobe during odor presentation

Odorant processing presents multiple parallels across animal species, and insects became relevant models for the study of olfactory coding because of the tractability of the underlying neural circuits. Within the insect brain, odorants are received by olfactory sensory neurons and processed by the antennal lobe network. Such a network comprises multiple nodes, named glomeruli, that receive sensory information and are interconnected by local interneurons participating in shaping the neural representation of an odorant. The study of functional connectivity between the nodes of a sensory network in vivo is a challenging task that requires simultaneous recording from multiple nodes at high temporal resolutions. Here, we used fast two-photon microscopy to follow the calcium dynamics of antennal lobe glomeruli and applied Granger causality analysis to assess the functional directed connectivity among network nodes during and after olfactory stimulation. Our findings show that there is a significant causal coupling between network nodes also in the absence of olfactory stimulation. However, connectivity patterns change upon odorant arrival, showing an increase in connection density and conveying odorant-specific information. Furthermore, we show that causal functional connectivity is unique in individual subjects, and cannot be detected upon artificial glomerular scrambling across individuals. This demonstrates that network states do not consist solely of correlations of mean glomerular responses, which are known to be conserved across bees.

neuroscience↗

bioRxiv2019

Coding of odour and space in the hemimetabolous insect Periplaneta americana

The general architecture of the olfactory system is highly conserved from insects to humans, but neuroanatomical and physiological differences can be observed across species. The American cockroach, inhabiting dark shelters with a rather stable olfactory landscape, is equipped with long antennae used for sampling the surrounding air-space for orientation and navigation. The antennaes exceptional length provides a wide spatial working range for odour detection; however, it is still largely unknown whether and how this is also used for mapping the structure of the olfactory environment. By selective labelling antennal lobe projection neurons with a calcium sensitive dye, we investigated the logic of olfactory coding in this hemimetabolous insect. We show that odour responses are stimulus-specific and concentration-dependent, and that structurally related odorants evoke physiologically similar responses. By using spatially confined stimuli, we show that proximal stimulations induce stronger and faster responses than distal ones. Spatially confined stimuli of the female pheromone periplanone-B activate sub-region of the male macroglomerulus. Thus, we report that the combinatorial logic of odour coding deduced from holometabolous insects applies also to this hemimetabolous species. Furthermore, a fast decrease in sensitivity along the antenna, not supported by a proportionate decrease in sensillar density, suggests a neural architecture that strongly emphasizes neuronal inputs from the proximal portion of the antenna. Summary statementBy selective labelling the cockroachs antennal lobe output neurons, we investigated the logic of olfactory coding in a hemimetabolous insect, showing that odour responses are stimulus-specific, concentration-dependent, and preserve information on the spatial structure of the stimulus.

neuroscience↗

bioRxiv2019

Exploring multiple sensory systems in ovipositors of Drosophila suzukii and related species with different egg-laying behaviour

Drosophila suzukii is an invasive agricultural pest species that lays eggs in fruit during ripening, while most closely related Drosophila species use rotten matter as oviposition substrates. This behaviour is allowed by an enlarged and serrated ovipositor that can pierce intact fruit skin. D. suzukii combines multiple sensory systems (mechanosensation, olfaction, and taste) to select oviposition sites. Here, we test the hypothesis that the D. suzukii ovipositor is involved in these sensory modalities. We first investigate the ovipositor gene expression using a comparative framework of four Drosophila species with gradual changes in ovipositor morphology to identify evolutionary adaptations specific to D. suzukii. Results show transcription of chemoreceptors and mechanoreceptors in the four species, with a common core of sensory receptors expressed in all of them. Then, we demonstrate that sensory structures present in the distal tip of the D. suzukii ovipositor are mechanosensory-like sensilla, and that the degenerin/epithelial sodium channel ppk is expressed in homologous structures in Drosophila melanogaster. Our results suggest the D. suzukii ovipositor playing a role in mechanosensation, which might be shared with other Drosophila species.

zoology↗