Biology subjects

Bore, A.

Publications and source records attributed to Bore, A..

11 recordsLinked to original sources

bioRxiv2026

sf-pediatric: A robust and age-adaptable end-to-end pipeline for pediatric diffusion MRI

Diffusion MRI (dMRI) provides a powerful, non-invasive window into white matter (WM) development. Yet, most existing processing pipelines are not well-suited to the rapidly evolving neurophysiology of the pediatric brain. Here, we introduce sf-pediatric, a scalable, end-to-end, age-adaptable dMRI pipeline that integrates normative models of brain diffusivities to enable optimal subject-specific analysis from birth through 18 years old. Leveraging normative trajectories derived from nearly 2,000 participants from six cohorts, sf-pediatric dynamically calibrates diffusion priors, template selection, segmentation, and WM atlases based on the subjects age. By incorporating automatic quality control into a portable, tested, containerized, open-access, and press-button framework across computing environments, sf-pediatric provides a robust pipeline for large-scale pediatric dMRI studies. We validated this approach by showing improved local modeling and cortical fanning while preserving reproducibility and the ability to derive brain-behavior relationships. Additionally, we demonstrated robust recovery of known developmental trajectories of WM microstructure and connectome-derived network organization.

neuroscience↗

bioRxiv2026

The FANCM-RMI1/2 complex promotes genomic instability and PARP inhibitor sensitivity in BRCA2-deficicient cells.

Cancer cells lacking BRCA1 or BRCA2 must adapt to survive and proliferate despite defective DNA repair and high genomic instability. Restoration of homologous recombination (HR) through loss of DNA end protection rescues growth defects and promotes PARP inhibitor (PARPi) resistance in BRCA1-deficient cells; however, the genetic basis of adaptation to BRCA2 loss remains largely unexplored. To delineate BRCA1- and BRCA2-specific adaptation trajectories, we established a fully isogenic screening platform in mouse embryonic stem cells engineered for acute depletion of either protein. This approach uncovered hundreds of genes with shared, distinct, or even opposing effects between the two BRCA-deficiency states. We identified FANCM and its interacting partners RMI1/2, CENPS/MHF1, CENPX/MHF2, and FAAP24 as essential in BRCA1-deficient cells but toxic in BRCA2-deficient contexts. Loss of FANCM in BRCA2-deficient cells alleviated genomic instability and proliferation defects by preventing RMI1/2-dependent replication fork degradation, without rescuing HR. Moreover, we show that the FANCM-RMI1/2 complex drives PARPi sensitivity in both mouse and human BRCA2-deficient cells, in contrast to the 53BP1-SHLD-CST axis in BRCA1-deficient cells. These findings reveal distinct adaptation routes to BRCA1 and BRCA2 loss and establish FANCM as a determinant of BRCA2-specific vulnerability and therapeutic response, with direct implications for tailoring prevention and therapy according to BRCA mutation status.

cancer biology↗

bioRxiv2025

Resting-state functional MRI derivatives: A dataset derived from the The Comprehensive Assessment of Neurodegeneration and Dementia Study

Resting-state functional connectivity (RSFC) holds promise for the detection and characterisation of dementia. The Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS-ND) Study, by the Canadian Consortium on Neurodegeneration in Aging (CCNA), provides a unique resource to study deeply phenotyped neurodegenerative conditions. We present RSFC derivatives for 784 participants (data release 7 of the cohort) who were either cognitively unimpaired or diagnosed primarily with Alzheimers disease (AD), mixed dementia (AD with a vascular component), mild cognitive impairment (MCI), vascular MCI, frontotemporal dementia, Parkinsons disease with or without MCI or dementia, Lewy body disease or subjective cognitive impairment. Functional MRI scans were preprocessed using fMRIPrep, and time-series and whole-brain connectomes generated using three atlases at multiple resolutions, denoised using seven different techniques. High-motion artifacts were managed using a liberal quality control threshold appropriate for an older clinical population, resulting in data from 680 participants. These derivatives are made available to the research community to accelerate research on RSFC biomarkers of neurodegenerative disease, reducing duplication of effort, saving computational resources, and improving standardisation across studies.

neuroscience↗

bioRxiv2024

A Genome-wide CRISPR screen unveils WDR91 protein as a promoter of productive ASO activity

Antisense oligonucleotides (ASOs) belong to promising therapeutics for the treatment of neurologic, muscular and metabolic disorders. Several ASOs have been approved so far and more than a hundred clinical trials are currently underway covering a dozen therapeutic areas. Yet, the mechanisms of internalization and cell trafficking of these molecules remain poorly understood. Moreover, with only a small fraction of ASOs reaching the correct cellular compartment following systemic delivery, the majority of targeted diseases requires recurrent injections of ASOs. A deeper understanding of these mechanisms would guide the improvement of their potency and thus, reduce the amount of delivered ASOs and their potential side-effects. Here, using a CRISPR screen, we investigated intracellular proteins involved in ASOs efficiency using a whole genome approach and identified several potential regulators which could significantly impact ASOs potency in melanoma cells. We validated WD Repeat Domain 91 (WDR91), a regulator of endosomal maturation, as a modulator whose depletion significantly inhibits ASO productive activity. This study provides the first list of ASO modulators using a biologically relevant assay to estimate the role of these proteins. In conclusion, these data could lead to a better understanding of the mechanisms favoring productive uptake or improved endosomal escape of ASOs.

molecular biology↗

bioRxiv2022

Clustering and temporal organization of sleep spindles underlie motor memory consolidation

Sleep benefits motor memory consolidation, which is mediated by sleep spindle activity and associated memory reactivations during non-rapid eye movement (NREM) sleep. However, the particular role of NREM2 and NREM3 sleep spindles and the mechanisms triggering this memory consolidation process remain controversial. Here, simultaneous electroencephalographic and functional magnetic resonance imaging (EEG-fMRI) recordings were collected during night-time sleep following the learning of a motor sequence task. Adopting a time-based clustering approach, we provide evidence that spindles iteratively occur within clustered and temporally organized patterns during both NREM2 and NREM3 sleep. However, the clustering of spindles in trains is related to motor memory consolidation during NREM2 sleep only. Altogether, our findings suggest that spindles clustering and rhythmic occurrence during NREM2 sleep may serve as an intrinsic rhythmic sleep mechanism for the timed reactivation and subsequent consolidation of motor memories, through synchronized oscillatory activity within a subcortical-cortical network involved during learning.

neuroscience↗

bioRxiv2021

TractoInferno: A large-scale, open-source, multi-site database for machine learning dMRI tractography

TractoInferno is the worlds largest open-source multi-site tractography database, including both research- and clinical-like human acquisitions, aimed specifically at machine learning tractography approaches and related ML algorithms. It provides 284 datasets acquired from 3T scanners across 6 different sites. Available data includes T1-weighted images, single-shell diffusion MRI (dMRI) acquisitions, spherical harmonics fitted to the dMRI signal, fiber ODFs, and reference streamlines for 30 delineated bundles generated using 4 tractography algorithms, as well as masks needed to run tractography algorithms. Manual quality control was additionally performed at multiple steps of the pipeline. We showcase TractoInferno by benchmarking the learn2track algorithm and 5 variations of the same recurrent neural network architecture. Creating the TractoInferno database required approximately 20,000 CPU-hours of processing power, 200 man-hours of manual QC, 3,000 GPU-hours of training baseline models, and 4 Tb of storage, to produce a final database of 350 Gb. By providing a standardized training dataset and evaluation protocol, TractoInferno is an excellent tool to address common issues in machine learning tractography.

neuroscience↗

bioRxiv2021

Longitudinal high-resolution imaging through a flexible intravital imaging window

Intravital microscopy (IVM) is a powerful technique that enables imaging of internal tissues at (sub)cellular resolutions in living animals. Here, we present a silicone-based imaging window consisting of a fully flexible, suture-less design that is ideally suited for long-term, longitudinal IVM of growing tissues and tumors. Crucially, we show that this window, without any customization, is suitable for numerous anatomical locations in mice using a rapid and standardized implantation procedure. This low-cost device represents a substantial technological and performance advance that facilitates intravital imaging in diverse contexts in higher organisms, opening new avenues for in vivo imaging of soft and fragile tissues. One-sentence summaryThis study presents a versatile, fully flexible imaging window that acts as an implantable transparent second skin for small laboratory animal in vivo imaging.

cell biology↗

bioRxiv2020

TractoFlow-ABS (Atlas-Based Segmentation)

In Diffusion MRI (dMRI), pathological brains are a challenge for tractography processing, where most pipelines are not are not robust to white matter lesions. Intensity of white matter lesions on T1 images can have similar contrasts to gray matter tissue, which leads to misclassifications or "holes" in the white matter mask. These holes produce premature stop for tracking algorithms. To handle these issues, we developed TractoFlow-ABS (Atlas-Based Segmentation). TractoFlow-ABS uses the Freesurfer atlas to compute tissue masks instead of FSL fast in standard TractoFlow. TractoFlow-ABS is therefore a derived version of TractoFlow that is robust to white matter anomalies such as hyperintensities and lesions.

neuroscience↗

bioRxiv2019

TractoFlow: A robust, efficient and reproducible diffusion MRI pipeline leveraging Nextflow & Singularity

A diffusion MRI (dMRI) tractography processing pipeline should be: i) reproducible in immediate test-test, ii) reproducible in time, iii) efficient and iv) easy to use. Two runs of the same processing pipeline with the same input data should give the same output today, tomorrow and in 2 years. However, processing dMRI data requires a large number of steps (20+ steps) that, at this time, may not be reproducible between runs or over time. If parameters such as the number of threads or the random number generator are not carefully set in the brain extraction, registration and fiber tracking steps, the end tractography results obtained can be far from reproducible and limit brain connectivity studies. Moreover, processing can take several hours to days of computation for a large database, even more so if the steps are running sequentially.\n\nTo handle these issues, we present TractoFlow, a fully automated pipeline that processes datasets from the raw diffusion weighted images (DWI) to tractography. It also outputs classical diffusion tensor imaging measures (fractional anisotropy (FA) and diffu-sivities) and several HARDI measures (Number of Fiber Orientation (NuFO), Apparent Fiber Density (AFD)). The pipeline requires a DWI and T1-weighted image as NIfTI files and b-values/b-vectors in FSL format. An optional reversed phase encoded b=0 image can also be used. This pipeline is based on two technologies: Nextflow and Singularity, as well as recommended pre-processing and processing steps from the dMRI community. In this work, the TractoFlow pipeline is evaluated on three databases and shown to be efficient and reproducible from 98% to 100% depending on parameter choices. For example, 105 subjects from the Human Connectome Project (HCP) were fully ran in twenty-five (25) hours to produce, for each subject, a whole-brain tractogram with 4 million streamlines. The contribution of this paper is to introduce the importance of a robust pipeline in terms of runtime and reproducibility over time. In the era of open data and open science, efficiency and reproducibility is critical in neuroimaging projects. Our TractoFlow pipeline is publicly available for academic research and is an important step forward for better structural brain connectivity mapping.

neuroscience↗

bioRxiv2019

Rice bran supplementation modulates growth, microbiome and metabolome in weaning infants: a clinical trial in Nicaragua and Mali

Rice bran supplementation provides nutrients, prebiotics and phytochemicals that enhance gut immunity, reduce enteric pathogens in mice and diarrhea in neonatal pigs, and warranted attention for improvement of environmental enteric dysfunction (EED) in children at risk. EED is a condition that drives childhood stunting via intestinal dysbiosis and impaired nutrient metabolism. This study investigated effects of rice bran supplementation on growth, EED biomarkers, gut microbiome and metabolome in weaning infants from 6 to 12 months old in Nicaragua and Mali. Healthy infants were randomized to a control group or rice bran group that received daily supplementation at increasing doses each month. Stool microbiomes were characterized using 16S rDNA amplicon sequencing. Stool metabolomes were analyzed using ultra-high-performance liquid-chromatography tandem mass-spectrometry. Statistical comparisons were completed at 6, 8, and 12 months of age. Daily consumption of rice bran was safe and feasible for infant growth, decreasing alpha-1 antitrypsin levels, and modulating gut microbiome and metabolome when compared to control. Rice bran merits investigation as a practical intervention strategy that could decrease EED prevalence and risk for children from low- and middle-income countries where rice is grown as a staple food, and bran is used as animal feed or wasted. One Sentence SummaryDietary rice bran supplementation during infant weaning from 6-12 months of age improved growth outcomes, modulated environmental enteric dysfunction biomarkers, and supported metabolism by the gut microbiome. The authors declare no competing financial or non financial interests to disclose as defined by Nature Research. There are also no other interests that might be perceived to influence the results and/or discussion reported in this paper. Correspondence and requests for materials should be addressed to Dr. Elizabeth Ryan (e.p.ryan@colostate.edu).

clinical trials↗

bioRxiv2016

Tractography-based connectomes are dominated by false-positive connections

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

neuroscience↗