Biology subjects

Sein, J.

Publications and source records attributed to Sein, J..

17 recordsLinked to original sources

bioRxiv2024

CIWARS: a web server for waterborne antibiotic resistance surveillance using longitudinal metagenomic data

The rise of antibiotic resistance (AR) is a major global health crisis, exacerbated by the overuse and misuse of antibiotics, leading to the rapid spread of antibiotic resistance genes (ARGs) in bacterial pathogens. This phenomenon poses significant threats to human and animal health, food security, and economic stability. Water bodies, particularly wastewater treatment plants (WWTPs), serve as critical reservoirs for ARGs, creating environments that favor the proliferation of resistant bacteria. Wastewater-based surveillance (WBS) has emerged as a cost-effective strategy for monitoring AR at the population level, providing real-time data to guide public health and policy decisions. Despite advancements in WBS, there are no comprehensive online analytical platforms for continuous environmental AR surveillance. This paper introduces CIWARS, a web server designed for AR analyses of longitudinal metagenomic data. CIWARS offers comprehensive ARG profiling, taxonomic annotation, and anomalous AR risk points detection. We demonstrate its capabilities through an interactive temporal data visualization, showcasing its potential for enhancing AR risk monitoring and guiding effective mitigation strategies. CIWARS is broadly applicable to longitudinal metagenomic data generated from any environment and aims to support global efforts in addressing the AR crisis by providing cyberinfrastructure for continuous AR surveillance. The web server is freely available at https://ciwars.cs.vt.edu/.

bioinformatics↗

bioRxiv2024

From movements to words: action monitoring in the medial frontal cortex along a caudal to rostral prediction error gradient

Speech error monitoring recruits the medial frontal cortex (MFC) region in the human brain. Error monitoring-related activity in the MFC has been interpreted both in terms of conflict monitoring and feedback-driven control, but as similar regions of the MFC are implicated in various levels of behavioral control ranging from basic motor movement control to high-level cognitive control functions, a more comprehensive account is needed. Moreover, as speech errors and other actions that involve varying control demands engage a widespread yet partially overlapping set of regions of the MFC, such an account should ideally explain the anatomical distribution of error-related functional activations within the MFC. Here we wanted to assess the hypothesis that the MFC has a similar role in the evaluation of action outcomes for motor and mental actions, operating along a rostral-caudal gradient of higher-lower level control demands involving prediction errors from both sensory and epistemic sources. To this end, we conducted an individual-specific annotation of task-fMRI BOLD activation peaks related to speech errors versus correct productions (i.e. that involve the largest cognitive control demands, Study I and II), tongue movement monitoring (i.e. that involve an intermediate level of cognitive and motor control demands) and tongue movement (i.e. that involve only motor control demands, Study II) in the MFC region. Results revealed overlapping clusters across the three contrasts across the MFC, but importantly both the number of peaks and their relative position along the rostral caudal axis were consistent with a hierarchical rostral caudal processing gradient in the MFC. While tongue movement showed more caudal activation in the MFC, speech errors showed more rostral activation, and tongue movement monitoring patterned in between. Furthermore, the combined results of both studies suggested that activation peaks were located more dorsally for participants that had a paracingulate gyrus, replicating a previously documented effect for movement and further supporting a common functional role of the MFC across very distinct actions.

neuroscience↗

bioRxiv2024

Congruent brain signatures specific to speech sounds in fronto-temporal cortex during language production and understanding.

In this fMRI study we investigated whether language production and understanding recruit the same phoneme-specific networks. We did so by comparing the brains response to different phoneme categories in minimal pairs: Bilabial-initial words (e.g., monkey) were contrasted to alveolar-initial words (e.g., donkey) in 37 participants performing both language production and comprehension tasks. Region-of-Interest analyses showed that the same sensorimotor networks were activated across the language modalities. In motor regions, word production and comprehension elicited the same phoneme-specific topographical activity patterns, with stronger haemodynamic activations for alveolar-initial words in the tongue cortex and stronger activations for bilabial-initial words in the lip cortex. In the posterior and middle superior temporal cortex, production and comprehension likewise resulted in similar activity patterns, with enhanced activations to alveolar-compared to bilabial-initial words. These results disagree with the classical separation between language production and understanding in neurobiological models of language, and instead advocate for a cortical organization where the same phoneme-specific acoustic-and-articulatory representations carry production and comprehension.

neuroscience↗

bioRxiv2024

Revealing the co-existence of written and spoken language coding neural populations in the left-ventral occipitotemporal cortex

Reading relies on the ability to map written symbols with speech sounds. The left ventral occipitotemporal cortex (left-vOT) plays a crucial role in this process. Through the automatization of the mapping ability, this specific part of the ventral visual pathway (a.k.a., the Visual Word Form Area) progressively becomes specialized in written word recognition. Yet, despite its key role in reading, the area also responds to speech. This observation raises questions about the actual nature of neural representations encoded in the left-vOT and, therefore, the underlying mechanism of the cross-modal responses. Here, we addressed this issue by applying fine-grained analyses of within- and cross-modal repetition suppression effects (RSEs) and Multi-Voxel Pattern Analyses in fMRI and sEEG experiments. Convergent evidence across analysis methods and protocols showed significant RSEs and successful decoding in both within-modal visual and auditory conditions suggesting that subpopulations of neurons within the left-vOT distinctly encode written and spoken language inputs. This functional organization of neural populations enables the area to respond to speech input directly and indirectly, i.e., after speech sounds are converted to orthographic representations. The finding opens further discussions on how the human brain may be prepared and adapted for an acquisition of a complex ability such as reading. Significance StatementLearning to read generates new functional responses in neurons in the left ventral visual pathway. Soon after reading acquisition, these neurons become specialized in processing known scripts, thus leading to the functional designation of the "Visual Word Form Area" (VWFA). However, controversies remain regarding the nature of neural representations encoded in this "reading" region, as its activation to speech is also reported. We investigate the neural mechanism(s) underlying these bimodal responses using within and cross-modal repetition suppression and decoding protocols. fMRI and sEEG experiments provided converging evidence indicating that, despite its specialization in reading, VWFA also contained subpopulations of neurons that encode speech. This functional organization could reveal why neurons at this anatomical location are ideal for reading acquisition.

neuroscience↗

bioRxiv2024

Reconstructing Voice Identity from Noninvasive Auditory Cortex Recordings

The cerebral processing of voice information is known to engage, in human as well as non-human primates, "temporal voice areas" (TVAs) that respond preferentially to conspecific vocalizations. However, how voice information is represented by neuronal populations in these areas, particularly speaker identity information, remains poorly understood. Here, we used a deep neural network (DNN) to generate a high-level, small-dimension representational space for voice identity--the voice latent space (VLS)--and examined its linear relation with cerebral activity via encoding, representational similarity, and decoding analyses. We find that the VLS maps onto fMRI measures of cerebral activity in response to tens of thousands of voice stimuli from hundreds of different speaker identities and better accounts for the representational geometry for speaker identity in the TVAs than in A1. Moreover, the VLS allowed TVA-based reconstructions of voice stimuli that preserved essential aspects of speaker identity as assessed by both machine classifiers and human listeners. These results indicate that the DNN-derived VLS provides high-level representations of voice identity information in the TVAs.

neuroscience↗

bioRxiv2024

Argon neuroprotection in a non-human primate model of transient endovascular ischemic stroke.

BackgroundPrevious studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present study was to confirm a potential neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke as an essential step before considering the use of argon as a neuroprotective agent in humans. MethodsThirteen adult monkeys (Macaca mulatta) were allocated to two groups: a control group (n=8) without neuroprotection and an argon group (n=5) in which argon inhalation (90 min) was initiated 30 minutes after onset of ischemia. Animals in both groups underwent brain MRI (pre-ischemic) at least 7 days before the intervention. The monkeys were subjected to focal cerebral ischemia induced by a transient (90 min) middle cerebral artery occlusion (tMCAO). After tMCAO, MRI was performed 1 hour after cerebral reperfusion. The ischemic core volume was defined by the apparent diffusion coefficient (aDC) and edema in fluid attenuated inversion recovery (FLAIR) acquisitions. MRI masks were applied to distinguish between cortical and subcortical abnormalities. In addition, a modified version of the Rankin scale was used to neurologically assess post-tMCAO. ResultsDespite variability in the ischemic core and edema volumes in the control group, argon significantly reduced ischemic core volume after ischemia compared to the control group (1.1{+/-}1.6 cm3 vs. 8.5{+/-}8.1 cm3; p=0.03). This effect was limited to cortical structures (0.6{+/-}1.1 cm3 vs. 7.4{+/-}7.2 cm3; p=0.03). No significant differences were observed in the edema volumes. Measures of neurological clinical outcome suggested a better prognosis in argon-treated animals. ConclusionsIn the tMCAO macaque model, argon induced effective neuroprotective effects, leading to a reduced ischemic core in cortical areas. These results support the potential use of this therapeutic approach for future clinical studies in stroke patients.

neuroscience↗

bioRxiv2023

Social Context and Drug Cues Modulate Inhibitory Control in Cocaine Addiction: involvement of the STN evidenced through Functional Magnetic Resonance Imaging

BackgroundAddictions often develop in a social context, although the influence of social factors did not receive much attention in the neuroscience of addiction. Recent animal studies suggest that peer presence can reduce cocaine intake, an influence potentially mediated, among others, by the subthalamic nucleus (STN). However, there is to date no such neurobiological study in humans. MethodsThis study investigated the impact of social context and drug cues on brain correlates of inhibitory control in individuals with and without cocaine use disorder (CUD) using functional Magnetic Resonance Imaging (fMRI). Seventeen CUD participants and 17 healthy controls (HC) performed a novel fMRI Stop-Signal task in the presence and absence of an observer while being exposed to cocaine-related and neutral pictures as cues. ResultsThe results showed that CUD participants, while slower at stopping with neutral cues, recovered control level stopping abilities with cocaine cues, while HC did not show any difference. Neuroimaging revealed the involvement of frontal cortical regions and of the subthalamic nucleus (STN) in inhibitory control, which was modulated by both social context and drug cues in CUD participants but not in HC. ConclusionsThese findings highlight the impact of social context and drug cues on inhibitory control in CUD and suggest potential targets for intervention such as the STN, also emphasizing the importance of considering the social context in addiction research and treatment.

neuroscience↗

bioRxiv2023

Auditory hemispheric asymmetry as a specialization for actions and objects

What is the function of auditory hemispheric asymmetry? We propose that the identification of sound sources relies on two complementary and perceptually relevant acoustic invariants -- actions and objects -- that are processed asymmetrically and sufficient to model and categorize any sound. We observed that environmental sounds are an independent combination of purely temporal and spectral acoustic modulations. Behaviorally, discrimination of actions relied on temporal modulations, while discrimination of objects relied on spectral modulations. Functional magnetic resonance imaging data showed that actions and objects are respectively decoded in the left and right hemispheres, in bilateral superior temporal and left inferior frontal regions. This asymmetry reffects a generic differential processing -- through differential neural sensitivity to temporal and spectral modulations present in all environmental sounds -- that supports the efficient categorization of actions and objects. These results provide an ecologically valid framework of the functional role of auditory brain asymmetry.

neuroscience↗

bioRxiv2022

Graph theoretical analysis reveals the adaptive role of the left ventral occipito-temporal cortex in the brain networks during speech processing

The left ventral occipito-temporal cortex (left-vOT) plays a key role in reading. Several studies have also reported its activation during speech processing, suggesting that it may play a role beyond written word recognition. Here, we adopt a graph theoretical analysis to investigate the functional role of this area in the whole-brain network while participants processed spoken sentences in different tasks. We find that its role and interactions with other areas changes in an adaptive manner. In a low-level speech perception task, the left-vOT is part of the visual network and acts as a connector that supports the communication with other cognitive systems. When speech comprehension is required, the area becomes a connector within the sensorimotor-auditory network typically recruited during speech processing. However, when comprehension is compromised due to degradation of speech input, the area disengages from the sensorimotor-auditory network. It becomes part of the visual network again and turns from connector into a simple peripheral node. These varying connectivity patterns are coherent with the Interactive Account considering the left-vOT as a convergent zone with multiple functions and interaction patterns that depend on task demands and the nature of sensory input.

neuroscience↗

bioRxiv2021

Planum Temporale grey matter volume asymmetries in new-born monkeys (Papio anubis)

The Planum Temporale (PT) is one of the key hubs of the language network in the human brain. The gross asymmetry of this perisylvian region toward the left brain was considered as the most emblematic marker of hemispheric specialization of language processes in the brain. Interestingly, this neuroanatomical signature was documented also in newborn infants and preterms, suggesting the early brains readiness for language acquisition. Nevertheless, this latter interpretation was questioned by a recent report in nonhuman primates of a potential similar signature in newborn baboons Papio anubis based on PT surface measures. Whether this "tip of the iceberg" PT asymmetry is actually reflecting asymmetry of its underlying grey matter volume remain unclear but critical to investigate potential continuities of cortical specialization with human infants. Here we report a population-level leftward asymmetry of the Planum Temporale grey matter volume in in vivo 34 newborn baboons Papio anubis, which showed intra-individual positive correlation with PT surfaces asymmetry measures but also a more pronounced degree of leftward asymmetry at the population-level. This finding demonstrates that PT leftward structural asymmetry in this Old World monkey species is a robust phenomenon in early primate development, which clearly speaks for a continuity with early human brain specialization. Results also strengthen the hypothesis that early PT asymmetry might be not a human-specific marker for the pre-wired language-ready brain in infants.

neuroscience↗

bioRxiv2020

Action Observation Network activity related to object-directed and socially directed actions in Adolescents

The Action Observation Network (AON) encompasses brain areas consistently engaged when we observe others actions. Although the core nodes of the AON are present from childhood, it is not known to what extent they are sensitive to different action features during development. As social cognitive abilities continue to mature during adolescence, the AON response to socially-oriented actions, but not to object-related actions, may differ in adolescents and adults. To test this hypothesis, we scanned with functional magnetic resonance imaging (fMRI) 28 typically-developing teenagers and 25 adults while they passively watched videos of hand actions varying along two dimensions: sociality (i.e. directed towards another person or not) and transitivity (i.e. involving an object or not). We found that observing actions recruited the same fronto-parietal and occipito-temporal regions in adults and adolescents. The modulation of voxelwise activity by the social or transitive nature of the action was similar in both groups of participants. Multivariate pattern analysis, however, revealed that the accuracy in decoding the social dimension from the brain activity patterns, increased with age in lateral occipital and parietal regions, known to be involved in semantic representations of actions, as well as in posterior superior temporal sulcus, a region commonly associated with perception of high level features necessary for social perception. Change in decoding the transitive dimension was observed only in the latter region. These findings indicate that the representation of others actions, and in particular their social dimensions, in the adolescent AON is still not as robust as in adults. Significance statementThe activity of the action observation network in the human brain is modulated according to the purpose of the observed action, in particular the extent to which it involves interaction with an object or another person. How this conceptual representation of actions is implemented during development is largely unknown. Here, using multivoxel pattern analysis of fMRI data, we discovered that, while the action observation network is in place in adolescence, the fine-grain organization of its posterior regions is less robust than in adults to decode the social or transitive dimensions of an action. This finding highlights the late maturation of social processing in the human brain.

neuroscience↗

bioRxiv2020

The cerebellum is involved in internal and external speech error monitoring

An fMRI study examined how speakers inspect their own speech for errors. In a word production task, we observed enhanced involvement of the right posterior cerebellum for trials that were correct, but on which participants were more likely to make a word-as compared to a non-word error. Furthermore, comparing errors to correctly produced utterances, we observed increased activation of the same cerebellar region, in addition to temporal and medial frontal regions. Within the framework associating the cerebellum to forward modelling of upcoming actions, this indicates that forward models of verbal actions contain information about word representations used for error monitoring even before articulation (internal monitoring). Additional resources relying on speech perception and conflict monitoring are deployed during articulation to detect overt errors (external monitoring). In summary, speech monitoring seems to recruit a network of brain regions serving domain general purposes, even for abstract levels of processing.

neuroscience↗

bioRxiv2020

A collaborative resource platform for non-human primate neuroimaging

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field.

neuroscience↗

bioRxiv2020

scReQTL: an approach to correlate SNVs to gene expression from individual scRNA-seq datasets

Recently, pioneering eQTLs studies on single cell RNA-seq (scRNA-seq) data have revealed new and cell-specific regulatory SNVs. Because eQTLs correlate genotypes and gene expression across multiple individuals, they are confined to SNVs with sufficient population frequency. Here, we present an alternative sc-eQTL approach - scReQTL - wherein we substitute the genotypes with expressed Variant Allele Fraction (VAFRNA) at heterozygous SNV sites. Our approach employs the advantage that, when estimated from multiple cells, VAFRNA can be used to assess effects of rare SNVs in a single individual. ScReQTLs are enriched in known genetic interactions, therefore can be used to identify novel regulatory SNVs.

genomics↗

bioRxiv2019

Estimating allele-specific expression of SNVs from 10x Genomics Single-Cell RNA-Sequencing Data

With the recent advances in single-cell RNA-sequencing (scRNA-seq) technologies, estimation of allele expression from single cells is becoming increasingly reliable. Allele expression is both quantitative and dynamic and is an essential component of the genomic interactome. Here, we systematically estimate allele expression from heterozygous single nucleotide variant (SNV) loci using scRNA-seq data generated on the 10x Genomics platform. We include in the analysis 26,640 human adipose-derived mesenchymal stem cells (from three healthy donors), with an average sequencing reads over 120K/cell (more than 4 billion scRNA-seq reads total). High quality SNV calls assessed in our study contained approximately 15% exonic and >50% intronic loci. To analyze the allele expression, we estimate the expressed Variant Allele Fraction (VAFRNA) from SNV-aware alignments and analyze its variance and distribution (mono- and bi-allelic) at different cutoffs for required minimal number of sequencing reads. Our analysis shows that when assessing SNV loci covered by a minimum of 3 unique sequencing reads, over 50% of the heterozygous SNVs show bi-allelic expression, while at minimum of 10 reads, nearly 90% of the SNVs are bi-allelic. Consistent with single cell studies on RNA velocity and models of transcriptional burst kinetics, we observe a substantially higher rate of monoallelic expression among intronic SNVs, signifying the usefulness of scVAFRNA to assess dynamic cellular processes. Our analysis demonstrates the feasibility of scVAFRNA estimation from current scRNA-seq datasets and shows that the 3-based library generation protocol of 10x Genomics scRNA-seq data can be highly informative in SNV-based analyses.

genomics↗

bioRxiv2019

RsQTL: correlation of expressed SNVs with splicing using RNA-sequencing data

RsQTL is a tool for identification of splicing quantitative trait loci (sQTLs) from RNA-sequencing (RNA-seq) data by correlating the variant allele fraction at expressed SNV loci in the transcriptome (VAFRNA) with the proportion of molecules spanning local exon-exon junctions at loci with differential intron excision (percent spliced in, PSI). We exemplify the method on sets of RNA-seq data from human tissues obtained though the Genotype-Tissue Expression Project (GTEx). RsQTL does not require matched DNA and can identify a subset of expressed sQTL loci. Due to the dynamic nature of VAFRNA, RsQTL is applicable for the assessment of conditional and dynamic variation-splicing relationships. Availability and implementationhttps://github.com/HorvathLab/RsQTL. Contacthorvatha@gwu.edu or jsein@gwmail.gwu.edu Supplementary InformationRsQTL_Supplementary_Data.zip

bioinformatics↗

bioRxiv2018

ReQTL - an allele-level measure of variation-expression genomic relationships

MotivationBy testing for association of DNA genotypes with gene expression levels, expression quantitative trait locus (eQTL) analyses have been instrumental in understanding how thousands of single nucleotide variants (SNVs) may affect gene expression. As compared to DNA genotypes, RNA genetic variation represents a phenotypic trait that reflects the actual allele content of the studied system. RNA genetic variation can be measured at expressed genome regions, and differs from the DNA genotype in sites subjected to regulatory forces. Therefore, assessment of correlation between RNA genetic variation and gene expression can reveal regulatory genomic relationships in addition to eQTLs.\n\nResultsWe introduce ReQTL, an eQTL modification which substitutes the DNA allele count for the variant allele frequency (VAF) at expressed SNV loci in the transcriptome. We exemplify the method on sets of RNA-sequencing data from human tissues obtained though the Genotype-Tissue Expression Project (GTEx) and demonstrate that ReQTL analyses show consistently high performance and sufficient power to identify both previously known and novel molecular associations. The majority of the SNVs implicated in significant cis-ReQTLs identified by our analysis were previously reported as significant cis-eQTL loci. Notably, trans ReQTL loci in our data were substantially enriched in RNA-editing sites. In summary, ReQTL analyses are computationally feasible and do not require matched DNA data, hence they have a high potential to facilitate the discovery of novel molecular interactions through exploration of the increasingly accessible RNA-sequencing datasets.\n\nAvailability and implementationSample scripts used in our ReQTL analyses are available with the Supplementary Material (ReQTL_sample_code).\n\nContacthorvatha@gwu.edu or lfspurr@gwmail.gwu.edu\n\nSupplementary InformationRe_QTL_Supplementary_Data.zip

genomics↗