Biology subjects

Lorenzi, C.

Publications and source records attributed to Lorenzi, C..

12 recordsLinked to original sources

bioRxiv2026

An integrated, transcript-resolution atlas of prostate cancer progression unmasks associations with oncogenic pathways

Most genes produce multiple non-coding and coding RNA transcripts with potentially divergent biological functions, yet their contribution to cancer remains largely unexplored. Here, we built an integrated, transcript-resolution RNA sequencing atlas of prostate cancer spanning 1,140 clinical samples from 10 independent studies, covering the full range of disease progression from normal tissue to primary, hormone-sensitive, and castration-resistant disease. Cross-study integration removes technical batch effects while retaining the biological heterogeneity that distinguishes these disease states, a property we validate against long-read sequencing and leverage to place newly incorporated external cohorts within this disease-progression context. We describe transcript patterns of oncogenic and tumor-suppressive long non-coding RNAs along disease progression and identify 41 protein-coding genes with significant isoform switches in cancer-relevant pathways, including WNT2B, RNF43, RELA, BRCA1, ROCK2, and TRIM11. Finally, we provide the Prostate Cancer Atlas (www.prostatecanceratlas.org), an interactive web resource that lets researchers contextualize their own transcriptomic data against this atlas.

cancer biology↗

bioRxiv2025

Auditory discrimination and identification of time of day for natural soundscapes

Following research on the auditory discrimination of natural soundscapes by human listeners [Apoux, Miller-Viacava, Ferriere, Dai, Krause, Sueur and Lorenzi (2023). J. Acoust. Soc. Am. 153, 2706], the present study assessed the ability of normal-hearing listeners to identify and/or discriminate the time of day (Dawn, Midday, Dusk, and Night) for soundscapes recorded in temperate and tropical forests. Identification was assessed using a single-interval four-alternative forced-choice task. Discrimination was assessed using a three-interval oddity task, where the listener was required to pick the odd one out. While identification of time of day was generally poor, discrimination was significantly above chance, indicating that listeners could hear some differences associated with the time of day, but could not effectively use those differences to assign the correct verbal label. The contribution of level, fine spectral, temporal envelope and temporal fine structure cues to discrimination was assessed. None of these cues appeared to be critical for time of day discrimination. Instead, it is suggested that listeners based their decisions on gross spectral cues, including aspects such as those related to ambient-noise spectral distributions.

ecology↗

bioRxiv2025

Targeting FOXA1 and FOXA2 Disrupts the Lineage-Specific Oncogenic Output Program in Prostate Cancer

Activation of the androgen receptor (AR) is the key lineage-specific oncogenic pathway and the primary therapeutic target in prostate cancer. While AR signaling is enabled by the pioneer transcription factor FOXA1, its homolog FOXA2 is specifically expressed in advanced lineage plasticity prostate cancers that have lost the AR signaling axis. However, their roles and utility as drug targets remain incompletely characterized. Here, we show an unexpected collaboration of FOXA1 and FOXA2 in mediating AR-independent cell proliferation in different lineage plasticity cancer subtypes. Conversely, joint loss-of-function or pharmacologic disruption of FOXA1 and FOXA2 leads to the collapse of lineage-specific oncogenic transcription factors followed by cell cycle arrest. In summary, our findings uncover a druggable dependency for AR-positive and - negative prostate cancers.

cancer biology↗

bioRxiv2025

Modulation statistics of natural soundscapes

Modulation statistics of "natural soundscapes" were estimated by calculating the modulation power spectrum (MPS) of a database of acoustic samples recorded in nine pristine terrestrial habitats for four moments of the day and two contrasting periods differing in precipitation level. Following Singh and Theunissen (2003), a set of statistics estimating low-pass quality, starriness, separability, asymmetry, modulation depth and [Formula] temporal-modulation power-law relationships were calculated from the MPS of the samples and related to geographical, meteorological factors and diel variations. MPS were found to be generally low-pass in shape in the modulation domain, with most of their modulation power restricted to low temporal (<10-20 Hz) and spectral modulations (<0.5-1 cycles/kHz). Modulation statistics distinguished between habitats irrespective of moment of the day and precipitation period, with a greater role of Modulation depth and Starriness. Separability and Starriness were found to be related to the global biodiversity decrease from tropical to polar regions, suggesting that the lack of joint high spectral and fast temporal modulations, and MPS complexity are important features characterising "biophony", the collective sound produced by animals in a given habitat. These findings may help guide research on monitoring auditory behaviors and underlying mechanisms expected to exploit regularities of natural scenes.

neuroscience↗

bioRxiv2020

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

In early embryogenesis of fast cleaving embryos DNA synthesis is short and surveillance mechanisms preserving genome integrity are inefficient implying the possible generation of mutations. We have analyzed mutagenesis in Xenopus laevis and Drosophila melanogaster early embryos. We report the occurrence of a high mutation rate in Xenopus and show that it is dependent upon the translesion DNA synthesis (TLS) master regulator Rad18. Unexpectedly, we observed a homology-directed repair contribution of Rad18 in reducing the mutation load. Genetic invalidation of TLS in the pre-blastoderm Drosophila embryo resulted in reduction of both the hatching rate and Single Nucleotide Variations on specific chromosome regions in adult flies. Altogether, these findings indicate that during very early Xenopus and Drosophila embryos TLS strongly contributes to the high mutation rate. This may constitute a previously unforeseen source of genetic diversity contributing to the polymorphisms of each individual with implications for genome evolution and species adaptation.

developmental biology↗

bioRxiv2020

A cell-to-patient machine learning transfer approach uncovers novel basal-like breast cancer prognostic markers amongst alternative splice variants

BackgroundBreast cancer is amongst the 10 first causes of death in women worldwide. Around 20% of patients are misdiagnosed leading to early metastasis, resistance to treatment and relapse. Many clinical and gene expression profiles have been successfully used to classify breast tumours into 5 major types with different prognosis and sensitivity to specific treatments. Unfortunately, these profiles have failed to subclassify breast tumours into more subtypes to improve diagnostics and survival rate. Alternative splicing is emerging as a new source of highly specific biomarkers to classify tumours in different grades. Taking advantage of extensive public transcriptomics datasets in breast cancer cell lines (CCLE) and breast cancer tumours (TCGA), we have addressed the capacity of alternative splice variants to subclassify highly aggressive breast cancers. ResultsTranscriptomics analysis of alternative splicing events between luminal, basal A and basal B breast cancer cell lines identified a unique splicing signature for a subtype of tumours, the basal B, whose classification is not in use in the clinic yet. Basal B cell lines, in contrast with luminal and basal A, are highly metastatic and express epithelial-to-mesenchymal (EMT) markers, which are hallmarks of cell invasion and resistance to drugs. By developing a semi-supervised machine learning approach, we transferred the molecular knowledge gained from these cell lines into patients to subclassify basal-like triple negative tumours into basal A- and basal B-like categories. Changes in splicing of 25 alternative exons, intimately related to EMT and cell invasion such as ENAH, CD44 and CTNND1, were sufficient to identify the basal-like patients with the worst prognosis. Moreover, patients expressing this basal B-specific splicing signature also expressed newly identified biomarkers of metastasis-initiating cells, like CD36, supporting a more invasive phenotype for this basal B-like breast cancer subtype. ConclusionsUsing a novel machine learning approach, we have identified an EMT-related splicing signature capable of subclassifying the most aggressive type of breast cancer, which are basal-like triple negative tumours. This proof-of-concept demonstrates that the biological knowledge acquired from cell lines can be transferred to patients data for further clinical investigation. More studies, particularly in 3D culture and organoids, will increase the accuracy of this transfer of knowledge, which will open new perspectives into the development of novel therapeutic strategies and the further identification of specific biomarkers for drug resistance and cancer relapse.

cancer biology↗

bioRxiv2020

A distributed network of noise-resistant neuronsin the central auditory system

Background noise strongly penalizes auditory perception of speech in humans or vocalizations in animals. Despite this, auditory neurons successfully detect and discriminate behaviorally salient sounds even when the signal-to-noise ratio is quite poor. Here, we collected neuronal recordings in cochlear nucleus, inferior colliculus, auditory thalamus, primary and secondary auditory cortex in response to vocalizations presented either against a stationary or a chorus noise. Using a clustering approach, we provide evidence that five behaviors exist at each level of the auditory system from neurons with high fidelity representations of the target, named target-specific neurons, mostly found in inferior colliculus and thalamus, to neurons with high fidelity representations of the noise, named masker-specific neurons mostly found in cochlear nucleus in stationary noise but in similar proportions in each structure in chorus noise. This indicates that the neural bases of auditory perception in noise rely on a distributed network along the auditory system.

neuroscience↗

bioRxiv2020

PickPocket : Pocket binding prediction for specific ligands family using neural networks.

Most of the protein biological functions occur through contacts with other proteins or ligands. The residues that constitute the contact surface of a ligand-binding pocket are usually located far away within its sequence. Therefore, the identification of such motifs is more challenging than the linear protein domains. To discover new binding sites, we developed a tool called PickPocket that focuses on a small set of user-defined ligands and uses neural networks to train a ligand-binding prediction model. We tested PickPocket on fatty acid-like ligands due to their structural similarities and their under-representation in the ligand-pocket binding literature. Our results show that for fatty acid-like molecules, pocket descriptors and secondary structures are enough to obtain predictions with accuracy >90% using a dataset of 1740 manually curated ligand-binding pockets. The trained model could also successfully predict the ligand-binding pockets using unseen structural data of two recently reported fatty acid-binding proteins. We think that the PickPocket tool can help to discover new protein functions by investigating the binding sites of specific ligand families. The source code and all datasets contained in this work are freely available at https://github.com/benjaminviart/PickPocket. Author SummaryMost of the protein biological functions are defined by its interactions with other proteins or ligands. The cavity of the protein structure that receives a ligand, also called a pocket, is made of residues that are usually located far away within its sequence. Therefore understanding the omplementarity of pocket and ligand is a real challenge. To discover new binding sites, we developed a tool called PickPocket that focuses on a small set of user-defined ligands to train a prediction model. Our results show that for fatty acid-like molecules, pocket descriptors (such as volume, shape, hydrophobicity...) and secondary structures are enough to obtain predictions with accuracy >90% using a dataset of 1740 manually curated ligand-binding pockets. The trained model could also successfully predict the ligand-binding pockets using unseen structural data of two recently reported fatty acid-binding proteins. We think that the PickPocket tool can help to discover new protein functions by investigating the binding sites of specific ligand families.

bioinformatics↗

bioRxiv2020

NF90 Modulates Processing of a Subset of Human Pri-miRNAs

MicroRNAs are predicted to regulate the expression of more than 60% of mammalian genes and play fundamental roles in most biological processes. Deregulation of miRNA expression is a hallmark of most cancers and further investigation of mechanisms controlling miRNA biogenesis is needed. The dsRNA-binding protein, NF90 has been shown to act as a competitor of Microprocessor for a limited number of pri-miRNAs. Here, we show that NF90 has a more widespread effect on pri-miRNA biogenesis than previously thought. Genome-wide approaches revealed that NF90 is associated with the stem region of 38 pri-miRNAs, in a manner that is largely exclusive of Microprocessor. Following loss of NF90, 22 NF90-bound pri-miRNAs showed increased abundance of mature miRNA products. NF90-targeted pri-miRNAs are highly stable, having a lower free energy and fewer mismatches compared to all pri-miRNAs. Mutations leading to less stable structures reduced NF90 binding while increasing pri-miRNA stability led to acquisition of NF90 association, as determined by RNA EMSA. NF90-bound and modulated pri-miRNAs are embedded in introns of host genes and expression of several host genes is concomitantly modulated. These data suggest that NF90 controls the processing of a subset of highly stable, intronic miRNAs.

molecular biology↗

bioRxiv2020

Mechanisms of spectrotemporal modulation detection for normal- and hearing-impaired listeners

Spectrotemporal modulations (STMs) offer a unified framework to probe suprathreshold auditory processing. Here, we introduce a novel methodological framework based on psychophysical reverse-correlation deployed in the modulation space to characterize how STMs are detected by the auditory system and how cochlear hearing loss impacts this processing. Our results show that young normal-hearing (NH) and older hearing-impaired (HI) individuals rely on a comparable non-linear processing architecture involving non-directional band-pass modulation filtering. We demonstrate that a temporal-modulation filter-bank model can capture the strategy of the NH group and that a broader tuning of cochlear filters is sufficient to explain the overall shift toward temporal modulations of the HI group. Yet, idiosyncratic behaviors exposed within each group highlight the contribution and the need to consider additional mechanisms. This integrated experimental-computational approach offers a principled way to assess supra-threshold auditory processing distortions of each individual.

neuroscience↗

bioRxiv2019

Cortical and subcortical neurons discriminate sounds in noise on the sole basis of acoustic amplitude modulations

Humans and animals maintain accurate sound discrimination in the presence of loud sources of background noise. It is commonly assumed that this ability relies on the robustness of auditory cortex responses. However, no attempt has been made to characterize neural discrimination of sounds masked by noise at each stage of the auditory system and disentangle the sub-effects of noise, namely the distortion of temporal cues conveyed by modulations in instantaneous amplitude and frequency, and the introduction of randomness (stochastic fluctuations in amplitude). Here, we measured neural discrimination between communication sounds masked by steady noise in the cochlear nucleus, inferior colliculus, auditory thalamus, primary and secondary auditory cortex at several signal-to-noise ratios. Sound discrimination by neuronal populations markedly decreased in each auditory structure, but collicular and thalamic populations showed better performance than cortical populations at each signal-to-noise ratio. Comparison with neural responses to tone-vocoded sounds revealed that the reduction in neural discrimination caused by noise was mainly driven by the attenuation of slow amplitude modulation cues, with the exception of the cochlear nucleus that showed a dramatic drop in discrimination caused by the randomness of noise. These results shed new light on the specific contributions of subcortical structures to robust sound encoding, and demonstrate that neural discrimination in the presence of background noise is mainly determined by the distortion of the slow temporal cues conveyed by communication sounds.

neuroscience↗

bioRxiv2017

Changes In Firing Regularity In The Normal And Impaired Auditory System

The auditory system processes temporal information at multiple scales, and disruptions to this temporal processing may lead to deficits in auditory tasks such as detecting and discriminating sounds in a noisy environment. Here, a modelling approach is used to study the temporal regularity of firing by chopper cells in the ventral cochlear nucleus, in both the normal and impaired auditory system. Chopper cells, which have a strikingly regular firing response, divide into two classes, sustained and transient, based on the time course of this regularity. Several hypotheses have been proposed to explain the behaviour of chopper cells, and the difference between sustained and transient cells in particular. However, there is no conclusive evidence so far. Here, a reduced mathematical model is developed and used to compare and test a wide range of hypotheses with a limited number of parameters. Simulation results show a continuum of cell types and behaviours: chopper-like behaviour arises for a wide range of parameters, suggesting that multiple mechanisms may underlie this behaviour. The model accounts for systematic trends in regularity as a function of stimulus level that have previously only been reported anecdotally. Finally, the model is used to predict the effects of a reduction in the number of auditory nerve fibres (deafferentation due to, for example, cochlear synaptopathy). An interactive version of this paper in which all the model parameters can be changed is available online.\n\nHighlightsO_LIA low parameter model reproduces chopper cell firing regularity\nC_LIO_LIMultiple factors can account for sustained vs transient chopper cell response\nC_LIO_LIThe model explains stimulus level dependence of firing regularity\nC_LIO_LIThe model predicts chopper cells fire more irregularly after deafferentation\nC_LIO_LIAn interactive version of the paper allows readers to change parameters\nC_LI

neuroscience↗