Biology subjects

Golan, T.

Publications and source records attributed to Golan, T..

11 recordsLinked to original sources

bioRxiv2026

Exploring per-base quality scores as a surrogate marker of cell-free DNA fragmentome

Per-base quality scores are widely treated as technical metadata in next-generation sequencing. Here, we show that in rigorously controlled whole-genome sequencing of cell-free DNA, quality profiles may encode fragmentomic signals that enable classification of cancer samples against matched controls. Analyzing four independent batches (23 cancer samples: pancreatic and breast; 22 matched controls) sequenced in a within-lane regime and further normalized per flow-cell tile to reduce technical confounders, we demonstrate through unsupervised analysis that boundary-enriched dynamics captured in these quality scores consistently separate cancer from control samples. A leave-one-batch-out classifier trained on quality-derived scores achieved a pooled area under the curve of 0.81. Furthermore, we show that the quality-derived metric correlates with short-fragment enrichment and tumor-associated 5-end motifs, performing comparably to established, motif-based orthogonal methods. These results provide initial evidence that quality scores could serve as a low-cost, alignment-free biomarker for cfDNA-based cancer detection. Key PointsO_LIPBQS in rigorously controlled cfDNA whole-genome sequencing contain biologically informative fragmentomic signal rather than only technical noise C_LIO_LIBoundary-enriched quality dynamics distinguish cancer samples from matched controls across independent sequencing batches C_LIO_LIA leave-one-batch-out classifier based on PBQS-derived features achieved a pooled AUC of 0.81 across 23 cancer and 22 control samples C_LIO_LIThe PBQS-derived score correlates with short-fragment enrichment and tumor-associated 5' end motifs, supporting its value as a lightweight orthogonal biomarker for cfDNA cancer. C_LI Biographical NoteProf. Noam Shomron heads the Functional Genomics Laboratory at Tel Aviv Universitys Medical School, where his group studies genomics and bioinformatics with a focus on sequencing technologies and translational medicine.

bioinformatics↗

bioRxiv2025

A Python Toolbox for Representational Similarity Analysis

Representational similarity analysis (RSA) is a method to characterize neural representations and evaluate computational models based on neural representational geometries. Here we present a wave of recent methodological advances, including improved measures of representational distances, evaluators for representational models, and statistical inference methods, which are available to the community in a new open-source toolbox in Python. The rsatoolbox enables neuroscientists to explore neural representational geometries and to evaluate neural network models, connecting theory to experiment in the new era of big models and big data.

neuroscience↗

bioRxiv2023

Emergence of brain-like mirror-symmetric viewpoint tuning in convolutional neural networks

Primates can recognize objects despite 3D geometric variations such as in-depth rotations. The computational mechanisms that give rise to such invariances are yet to be fully understood. A curious case of partial invariance occurs in the macaque face-patch AL and in fully connected layers of deep convolutional networks in which neurons respond similarly to mirror-symmetric views (e.g., left and right profiles). Why does this tuning develop? Here, we propose a simple learning-driven explanation for mirror-symmetric viewpoint tuning. We show that mirror-symmetric viewpoint tuning for faces emerges in the fully connected layers of convolutional deep neural networks trained on object recognition tasks, even when the training dataset does not include faces. First, using 3D objects rendered from multiple views as test stimuli, we demonstrate that mirror-symmetric viewpoint tuning in convolutional neural network models is not unique to faces: it emerges for multiple object categories with bilateral symmetry. Second, we show why this invariance emerges in the models. Learning to discriminate among bilaterally symmetric object categories induces reflection-equivariant intermediate representations. AL-like mirror-symmetric tuning is achieved when such equivariant responses are spatially pooled by downstream units with sufficiently large receptive fields. These results explain how mirror-symmetric viewpoint tuning can emerge in neural networks, providing a theory of how they might emerge in the primate brain. Our theory predicts that mirror-symmetric viewpoint tuning can emerge as a consequence of exposure to bilaterally symmetric objects beyond the category of faces, and that it can generalize beyond previously experienced object categories.

neuroscience↗

bioRxiv2022

Loss of tumor suppressor WWOX enhances RAS activity in pancreatic cancer

Pancreatic cancer is one of the most lethal cancers, owing to its late diagnosis and resistance to chemotherapy. The tumor suppressor WW domain-containing oxidoreductase (WWOX), one of the most active fragile sites in the human genome (FRA16D), is commonly altered in pancreatic cancer. However, the direct contribution of WWOX loss to pancreatic cancer development and progression remains largely unknown. Here, we report that combined conditional deletion of Wwox and activation of KRasG12D in Ptf1a-CreER-expressing mice results in accelerated formation of precursor lesions and pancreatic carcinoma. At the molecular level, we found that WWOX physically interacts with SMAD3 and BMP2, which are known activators of the TGF-{beta} signaling pathway. In the absence of WWOX, TGF{beta}/BMPs signaling was enhanced, leading to increased macrophage infiltration and enhanced cancer stemness. Finally, overexpression of WWOX in patient-derived xenografts led to diminished aggressiveness both in vitro and in vivo. Overall, our findings reveal an essential role of WWOX in pancreatic cancer development and progression and underscore its role as a bona fide tumor suppressor.

cancer biology↗

bioRxiv2021

BRCA mutational status shapes the stromal microenvironment of pancreatic cancer linking CLU+ CAF expression with HSF1 signaling

Cancer-associated fibroblasts (CAFs) give rise to desmoplastic stroma, which supports tumor progression and metastasis, and comprises up to 90% of the tumor mass in pancreatic cancer. Recent work by us and others has shown that CAFs are transcriptionally rewired by adjacent cancer cells to form heterogeneous subtypes. Whether this rewiring is differentially affected by different driver mutations in cancer cells is largely unknown. Here we address this question by dissecting and comparing the stromal landscape of BRCA-mutated and BRCA Wild-type (WT) pancreatic ductal adenocarcinoma (PDAC). We comprehensively analyze PDAC samples from a cohort of 42 patients by laser-capture microdissection, RNA-sequencing and multiplexed immunofluorescence, revealing different CAF subtype compositions in germline BRCA-mutated vs. BRCA-WT tumors. In particular, we detect an increase in a subset of Clusterin (CLU)-positive CAFs in BRCA-mutated tumors. We further unravel a network of stress responses upregulated in BRCA-mutated tumors. Using cancer organoids and cell co-cultures, we show that the transcriptional shift of pancreatic stellate cells into CLU+ CAFs is mediated through activation of heat-shock factor 1 (HSF1), the transcriptional regulator of Clu. Our findings unravel a new dimension of stromal heterogeneity, influenced by germline mutations in cancer cells, with direct translational implications for clinical research. SignificanceBRCA1/2 mutations initiate some of the deadliest cancers, yet the fibroblastic microenvironment of BRCA-mutated cancers remains uncharted. Our work addresses a major unsolved question - to what extent is the tumor microenvironment determined by cancer mutations? We find that BRCA mutations in the cancer cells affect the composition of CAFs in PDAC. These findings have direct implications for diagnosis and for efforts to exploit CAFs for therapy.

cancer biology↗

bioRxiv2020

Self-Supervised Natural Image Reconstruction and Rich Semantic Classification from Brain Activity

Reconstructing natural images and decoding their semantic category from fMRI brain recordings is challenging. Acquiring sufficient pairs of images and their corresponding fMRI responses, which span the huge space of natural images, is prohibitive. We present a novel self-supervised approach that goes well beyond the scarce paired data, for achieving both: (i) state-of-the art fMRI-to-image reconstruction, and (ii) first-ever large-scale semantic classification from fMRI responses. By imposing cycle consistency between a pair of deep neural networks (from image-to-fMRI & from fMRI-to-image), we train our image reconstruction network on a large number of "unpaired" natural images (images without fMRI recordings) from many novel semantic categories. This enables to adapt our reconstruction network to a very rich semantic coverage without requiring any explicit semantic supervision. Specifically, we find that combining our self-supervised training with high-level perceptual losses, gives rise to new reconstruction & classification capabilities. In particular, this perceptual training enables to classify well fMRIs of never-before-seen semantic classes, without requiring any class labels during training. This gives rise to: (i) Unprecedented image-reconstruction from fMRI of never-before-seen images (evaluated by image metrics and human testing), and (ii) Large-scale semantic classification of categories that were never-before-seen during network training. Such large-scale (1000-way) semantic classification from fMRI recordings has never been demonstrated before. Finally, we provide evidence for the biological consistency of our learned model.

neuroscience↗

bioRxiv2018

Widespread suppression of high-order visual cortex during blinks and external predictable visual interruptions

Spontaneous eye blinks generate frequent potent interruptions to the retinal input and yet go unnoticed. As such, they provide an attractive approach to the study of the neural correlates of visual awareness. Here, we tested the potential role of predictability in generating blink-related effects using fMRI. While participants attentively watched still images of faces and houses, we monitored naturally occurring spontaneous blinks and introduced three kinds of matched visual interruptions: cued voluntary blinks, self-initiated (and hence, predictable) external darkenings, and physically similar but unpredictable external darkenings. These events impact was inspected using fMRI across the visual hierarchy. In early visual cortex, both spontaneous and voluntary blinks, as well as predictable and unpredictable external darkenings, led to largely similar positive responses in peripheral representations. In mid- and high-level visual cortex, all predictable conditions (spontaneous blinks, voluntary blinks, and self-initiated external darkenings) were associated with signal decreases. In contrast, unpredictable darkenings were associated with signal increases. These findings suggest that general-purpose prediction-related mechanisms are involved in producing a small but widespread suppression of mid- and high-order visual regions during blinks. Such suppression may down-regulate responses to predictable transients in the human visual hierarchy.

neuroscience↗

bioRxiv2018

Specific detection of cell-free DNA derived from intestinal epithelial cells using methylation patterns

Epithelial cells of the intestine undergo rapid turnover and are thought to be cleared via stool. Disruption of tissue architecture, as occurs in colorectal cancer (CRC), results in the release of material from dying intestinal epithelial cells to blood. This phenomenon could be utilized for diagnosis and monitoring of intestinal diseases, if circulating cell-free DNA (cfDNA) derived from intestinal cells could be specifically identified. Here we describe two genomic loci that are unmethylated specifically in intestinal epithelial cells, allowing for sensitive and specific detection of DNA derived from such cells. As expected, intestinal DNA is found in stool, but not in plasma, of healthy individuals. Patients with inflammatory bowel disease (IBD) have minimal amounts of intestinal cfDNA in the plasma, whereas patients with advanced CRC show a strong signal. The intestinal markers are not elevated in plasma samples from patients with pancreatic ductal adenocarcinoma (PDAC), and a combination of intestine- and pancreas-specific markers allowed for robust differentiation between plasma cfDNA derived from CRC and PDAC patients. Intestinal DNA markers provide a mutation-independent tool for monitoring intestinal dynamics in health and disease.

developmental biology↗

bioRxiv2017

Repeated performance in problem-solving tasks attenuates human cortical responses

A ubiquitous characteristic of human cortical networks is their tendency to rapidly change their response properties upon repetition. While this phenomenon has been amply documented using simple sensory-motor tasks, it is still unclear to what extent brain activations change on a short time scale when we are engaged in high level, complex tasks. Here, we examined this question using three types of high-level visual problems. We analyzed data from intracranial recordings performed in eight patients, focusing on the location and type of changes and on their relationship to overt behavior. Our results show significant repetition effects, manifested as signal decrease with repetition, in three different groups of electrodes: Visual sites, which increased their activity during stimuli presentation; Processing Positive sites, which demonstrated increased activity throughout the experimental trial; and Processing Negative sites, which demonstrated suppression of activity during the trial as compared to baseline. Interestingly, despite these significant repetition effects, response time remained unchanged with repetition. These findings bear directly upon our ability to interpret results aggregated across multiple repetitions of the same complex task.

neuroscience↗

bioRxiv2017

Increasing Suppression Of Saccade-Related Transients Along The Human Visual Hierarchy

A key hallmark of visual perceptual awareness is robustness to instabilities arising from unnoticeable eye and eyelid movements. In previous human intracranial (iEEG) work (Golan et al., 2016) we found that excitatory broadband high-frequency activity transients, driven by eye blinks, are suppressed in higher-level but not early visual cortex. Here, we utilized the broad anatomical coverage of iEEG recordings in 12 eye-tracked neurosurgical patients to test whether a similar stabilizing mechanism operates following small saccades. We compared saccades (1.3{degrees}-3.7{degrees}) initiated during inspection of large individual visual objects with similarly-sized external stimulus displacements. Early visual cortex sites responded with positive transients to both conditions. In contrast, in both dorsal and ventral higher-level sites the response to saccades (but not to external displacements) was suppressed. These findings indicate that early visual cortex is highly unstable compared to higher-level visual regions which apparently constitute the main target of stabilizing extra-retinal oculomotor influences.

neuroscience↗

bioRxiv2016

Persistent neural activity encoding real-time presence of visual stimuli decays along the ventral stream

Neural populations that encode sensory experience should be persistently active for as long as the experience persists. However, research into visual neural activity has focused almost exclusively on onset-driven responses that cannot account for sustained perception. We used intracranial recordings in humans to determine the degree to which the presence of a visual stimulus is persistently encoded by neural activity. The correspondence between stimulus duration and response duration was strongest in early visual cortex and gradually diminished along the visual hierarchy, such that is was weakest in inferior-temporal category-selective regions. A similar posterior-anterior gradient was found within inferior temporal face-selective regions, with posterior but not anterior sites showing persistent face-selective activity. The results suggest that regions that appear uniform in terms of their category selectivity are dissociated by how they temporally represent a stimulus in support of real-time experience, and delineate a large-scale organizing principle of the ventral visual stream.

neuroscience↗