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Biology subjects

Levy, A.

Publications and source records attributed to Levy, A..

At least 19 recordsLinked to original sources
bioRxiv2026

Phloem-Limited Disease Impacts Citrus Carbohydrate Dynamics Distinctly from Source-Sink Manipulation

Source-sink dynamics are defined by the interdependence of source and sink tissues and are key determinants of plant growth and productivity. This dynamic can, be altered by disease. One example is huanglongbing (HLB), a phloem-limited disease that impacts several economically important tree species by disrupting carbon partitioning and altering source-sink relationships. Though HLB is widespread in citrus, the specific mechanism in which phloem disruption impacts the co-regulation of carbon dynamics from source to sink has not been fully described. To address this, we took advantage of a natural study under field conditions, in which infected and uninfected trees were growing in the same field. After identifying trees that were uninfected, infected with symptoms, or infected without symptoms, we manipulated source:sink ratio by girdling branches and defoliating at 0%, 50%, and 75% of the original leaf area per fruit, while leaving a control treatment with no defoliation or girdling and used fruits as the sink of interest. We measured gas exchange, biomass, and non-structural carbohydrates in leaves, stems and fruits in response to these treatments. Our results show that leaf photosynthetic responses to HLB were primarily driven by stomatal regulation rather than biochemical limitations. HLB increased leaf dark respiration without altering the relationship between respiration and leaf soluble sugars. Among the plant organs, stem starch reserves were the most responsive to source-sink manipulation and were strongly correlated with multiple carbon pools and biomass in both fruits and leaves. Although HLB altered fruit carbon dynamics, it did not change fruit responses to source-sink manipulation. Overall, HLB affects source and sink tissues independently of the experimental source-sink manipulation. The stem serves as a transient carbon reserve and is sensitive to both HLB and source-sink manipulation. These findings raise further questions regarding total carbon fluxes and the importance of feedback inhibition of photosynthesis.

plant biology↗
bioRxiv2026

HIV remodels germinal centers through T follicular helper cell loss

T follicular helper cells (Tfh) within germinal centers are among the most permissive cells for HIV infection and serve as a critical part of the viral reservoir. Given the key role of Tfh in affinity maturation and the production of plasma cells and memory B cells, an understanding of this critical viral reservoir is fundamental not only for cure strategies but also for understanding immunodeficiency in people living with HIV (PLWH). Using rare clinical specimens from PLWH, we demonstrate that HIV causes both a change in the cellular composition of germinal centers and changes in their overall architecture in ways that are consistent with the immunodeficiency seen in PLWH, independent of their CD4 count. We note a significant decrease in the number of GC Tfh cells and an increase in the number of follicular CD8 T cells in lymphoid tissues obtained from PLWH. Our data further show that GC size is decreased both by HIV and with increased age. Single-cell RNA sequencing data demonstrate that HIV acutely decreases the expression of Tfh B-cell support pathways and disrupts Tfh expression of cell trafficking receptors. Additionally, in a lymphoid organoid model of acute infection that forms GC-like structures, these findings are recapitulated, suggesting that New Approach Methodologies could be germane to understanding the impact of HIV on the reservoir and immunodeficiency. This study describes previously undocumented remodeling of the germinal center niche in PLWH, providing insight into the immune microenvironment of a key HIV reservoir that may help inform future cure strategies.

microbiology↗
bioRxiv2026

Kingdom-wide Discovery of Type VI Secretion Effectors via AI Uncovers Three New Bacterial Toxins

The type VI secretion system (T6SS) is a molecular harpoon used by 19% of bacteria to inject toxic proteins into microbial or host cells. Despite its widespread distribution, many T6SS effector (T6Es) genes remain unidentified. Here, we developed an XGBoost classifier integrating 42 genetic and biochemical features to identify novel T6Es. Applying our model to 2,559 T6SS-encoding bacterial genomes revealed 19,958 T6E candidates. We validated our computational predictions and confirmed that three effector candidates, having new 3D structures, demonstrated cytotoxicity to bacteria and yeast, mostly in the bacterial periplasm. For two of these, cognate immunity proteins neutralizing toxicity have been validated. T6EC11, a new peptidoglycan degrading effector, quickly leads to spherical E. coli, with inner membrane separation, and gradual peptidoglycan degradation in a unipolar manner, demonstrating an intriguing moon-like structural phenotype. T6EC12, an effector toxic to bacteria and yeast, carries a conserved zinc-binding motif. Mutations the motif markedly reduced toxicity, suggesting that T6EC12 represents a novel metalloprotease. Our study expands the known T6E repertoire, and provides thousands of T6E predictions in all T6SS-encoding bacteria.

microbiology↗
bioRxiv2026

Species-specific metabolic networks shape evolutionary routes to functional rescue

Metabolic networks are highly interconnected. Still, it remains unclear whether organism- and environment-specific factors shape their capacity to evolve in response to metabolic stress or whether it follows general principles. Here, we studied metabolic evolvability in Bacillus subtilis using auxotrophic mutants lacking central biosynthetic enzymes. Across two genetic backgrounds with contrasting biofilm-forming capacities and under direct or gradual selection through nutrient gradients, B. subtilis bypassed 9 of 17 essential functions. Rescue was more frequent in the biofilm-proficient background and under gradual selection, which was also associated with more mutations in coding regions, particularly nonsynonymous. Adaptation proceeded through loss-of-function mutations that relieved regulatory or enzymatic constraints and redirected metabolic flux. Comparison with Escherichia coli revealed substantial differences in bypassability and genetic routes that persisted under matched conditions, although two cross-species solutions converged at the pathway level. Our data show species-specific metabolic networks shape available rescue routes, while ecological context influences their evolutionary accessibility during adaptation.

evolutionary biology↗
bioRxiv2026

Conserved inhibitory mechanisms of root-associated bacteria towardsArabidopsis thaliana and Chlamydomonas reinhardtii

Soil bacteria colonize plants without causing visible disease, yet many suppress host growth. The prevalence and evolutionary reach of this cryptic inhibition are unknown, because phenotyping hundreds of isolates in plants is prohibitively slow. Here we use the unicellular algae Chlamydomonas reinhardtii as a scalable proxy for the green lineage. We screened 148 plant-associated bacteria on Chlamydomonas lawns. Seven of eight Chlamydomonas inhibitors also inhibited the vascular model plant Arabidopsis thaliana. In one of these dual inhibitors, Burkholderia sola MF6, transposon screening and proteomics implicated type VI secretion and tight-adherence pili, and over half the non-inhibitory mutants also failed against Arabidopsis. In the algae, infection triggers rapid deflagellation, then non-lytic regulated cell death. The algal zinc/iron transporter ZIP3 promotes inhibition, whereas the cathepsin X protease CEP12 restrains it, and ZIP3 is epistatic to CEP12. Cryptic inhibition is thus ancient and widespread, and a unicellular algae uncovers it at scale.

plant biology↗
bioRxiv2026

PhageTAILor leverages machine learning for phage tail-like elements detection and classification in plant-associated bacteria

Phage tail-like elements (PTEs) -- tailocins, bacterial type VI secretion systems (T6SS), and extracellular contractile injection systems (eCIS) -- are contractile nanomachines that bacteria use to kill their neighbors and compete within their micro-ecosystems. PTEs help shape microbial community composition. Most PTE detection tools only detect a single PTE class. Moreover, most tailocin detection methods are largely restricted to Pseudomonas, leaving a key part of tailocin diversity uncharacterized. In this work, we present PhageTAILor (https://github.com/hjcho-bio/PhageTAILor), an integrative and fully automated pipeline that detects and classifies prophages and 3 PTE classes from bacterial genomes. PhageTAILor combines a 6-detector homology-based candidate search (geNomad, tail-gene, PHROGs-tail, SecReT6, eCIStem, and a divergence-tolerant tail-HMM detector) with a LightGBM classifier comprising 1 multiclass and 3 binary heads, trained on 6,501 bacterial genomes carrying 13,082 prophages and PTEs. A phylogeny-free feature matrix used in our model keeps predictions reproducible between model construction and user inference. PhageTAILor performs strongly at the genome level and generalizes beyond its Pseudomonas-rich training set. On a 76-strain cross-clade benchmark, PhageTAILor detected tailocins at F1 = 0.955. Furthermore, it identified 12 of 13 experimentally validated tailocins spanning five genera versus 2 of 13 for a Pseudomonas-restricted tool TattleTail. PhageTAILor also demonstrated sensitivity equivalent to viral detection tool geNomad while avoiding its higher false-positive rate. Applied to 7,925 plant- and soil-associated bacterial isolates, PhageTAILor showed that prophages in the phyllosphere and tailocins in plant-associated bacteria, whereas eCIS are enriched in soil. PhageTAILor is distributed as an open-source, modular pipeline with a command-line interface.

microbiology↗
bioRxiv2026

A modular platform for scalable recombinant production of highly toxic bacterial proteins

Bacterial protein toxins constitute a vast and largely untapped reservoir of antimicrobial activities with substantial therapeutic and biotechnological potential. However, their intrinsic toxicity frequently prevents stable recombinant expression in bacterial hosts, creating a major bottleneck for biochemical characterization, structural analysis, and development as antimicrobial agents. Here, we present a modular platform for the scalable recombinant production of highly toxic bacterial proteins based on transient intramolecular toxin neutralization. The strategy covalently links each toxin to its cognate immunity protein, promoting neutralization during biosynthesis while permitting recovery of the native toxin through site-specific proteolytic cleavage. Using this approach, we produced multiple previously intractable polymorphic toxin domains that could not be obtained using conventional inducible expression, toxin-immunity co-expression, or bacterial cell-free systems. We further streamlined the production workflow through intracellular protease-mediated cleavage, reducing the purification process from four steps to two and increasing protein recovery. To address cases in which native immunity proteins were insufficient, we incorporated computational protein design to engineer improved toxin-binding partners, enabling production of an additional toxin that remained refractory to the original platform. Purified toxins retained enzymatic activity following denaturation and refolding, confirming recovery of functional proteins and enabling identification of a previously uncharacterized nuclease activity. Together, these findings establish a scalable and adaptable microbial biotechnology platform for the production of intrinsically toxic proteins. The integration of transient intramolecular neutralization with computational engineering provides a route toward systematic production and characterization of toxic proteins for antimicrobial discovery, structural biology, protein engineering, and future biotechnological applications.

biochemistry↗
bioRxiv2026

Event-Related Warping: A Toolbox for Temporal Alignment and Jitter Correction in Sequential Experimental Paradigms

Sequential experimental paradigms are fundamental to cognitive neuroscience, yet standard event-related response analysis struggles with the temporal variability inherent to these designs. Conventional epoching treats each event within a sequence as an independent response, discarding the temporal dependencies between successive events and obscuring systematic changes in neural state that accumulate across the sequence. In order to generate responses that capture the entire sequence, it necessitates alignment across trials to correct for the inherent temporal jitter that would otherwise blur averaged responses and obscure the true sequential dynamics. Existing temporal alignment methods warp observed signals directly, making them vulnerable to correlated noise and potentially disrupting multichannel temporal relationships essential for connectivity and causal analyses. Event-Related Warping (ERW) addresses these limitations by aligning template functions encoding experimental event structure rather than neural signals themselves. Templates constructed from event onsets and durations undergo smooth monotonic warping via gradient-based optimisation, then estimated trajectories are applied uniformly across all channels, preserving inter-channel timing relationships and causal structure. This design-level alignment exploits experimentally observable jitter whilst maintaining signal integrity. Simulations with known ground truth incorporating Gaussian jitter, skewed latencies, amplitude-latency coupling, and multi-parameter dependencies yielded standardised root-mean-square errors (sRMSE) of 0.27-0.38. Distance-weighted averaging, emphasising temporally consistent trials, provided 5-13% improvement when jitter exceeded 100 ms, with maximal benefit ({approx}13% reduction) under quadratic amplitude-latency coupling. Empirical validation using an auditory go/no-go dataset with cue-to-target intervals of 1.5-4.1 seconds demonstrated that ERW recovers jittered target-locked responses with comparable fidelity (sRMSE 0.24-0.51) to conventional epoching of time-locked events, whilst preserving inter-channel lag relationships (cross-covariance sRMSE 0.63-0.82). ERW thus extends standard trial averaging to scenarios where temporal variability would otherwise preclude coherent response recovery, supporting investigation of temporally extended processing in ecologically valid paradigms whilst maintaining compatibility with established ERP frameworks and downstream connectivity analyses.

neuroscience↗
bioRxiv2026

Predicting unknown binding sites for transition metal based compounds in proteins

Transition metal based compounds are promising therapeutic agents, particularly in cancer treatment. However, predicting their binding sites remains a major challenge. In this work, we investigate the applicability of two tools, Metal3D and Metal1D, for this purpose. Although originally trained to predict zinc ion binding sites only, both predictors successfully identify several experimentally observed binding sites for transition metal complexes directly from apo protein structures. At the same time, we highlight current limitations, such as the sensitivity to side-chain conformations, and discuss possible strategies for improvement. This work provides a first step toward establishing a robust computational pipeline in which rapid and low-cost predictors are able to identify putative hotspots for transition metal binding, which can then be refined using more accurate but computationally demanding methods. Author summaryTransition metals play a crucial role as therapeutic agents, especially in cancer therapy. However, the prediction of their binding site locations is challenging, as accurate computational methods often require time-consuming simulations, making them impractical when many possible binding sites must be explored. In this work, we explored the capability of two binding site predictors, originally developed to locate metal ions in proteins, to identify binding sites for more complex covalently-bound transition metal based agents. We found that these tools can often identify the experimentally-known binding regions, even when starting from the apo structure, in which the protein does not already contain the metal compound. At the same time, our results show clear limitations in more challenging cases, particularly when the binding involves only a single amino acid or when the binding site undergoes major structural rearrangements upon binding. Overall, our study shows that fast predictors can provide valuable early insights in the investigation of the binding sites of covalently-bound transition metal based compounds. When combined with more accurate simulation techniques, they can help focus computational efforts and ultimately support the rational design of transition metal based drugs.

bioinformatics↗
bioRxiv2026

Arabidopsis Membrane Contact Site protein SYNAPTOTAGMIN A maintains sieve element endomembrane morphology and function

Very little is known about the sieve element (SE) endomembrane system. In terms of surface area, the most important membrane is the SE endoplasmic reticulum, characterized by a unique cisternal structure of anchored flat and smooth stacks. Plasma membrane contact sites (MCSs) play a crucial role in anchoring the endoplasmic reticulum (ER) to the plasma membrane (PM) and in maintaining membrane intergrity. Here, we tested their role of MCSs in the endomembrane system of the sieve elements. Synaptotagmin A (SYTA) is one of the best-studied proteins known to form ER-PM MCSs in plants. We show that SYTA:RFP co-localizes with SUC2::GFP and CALS7::GFP, confirming its presence in Arabidopsis SEs. In syta-1 mutants, SER lost its discrete shape and separated from the SE wall. The export of 14C-compounds from leaves of wild type plants was about 10% higher than in syta-1 mutants. Finally, we explored SYTAs role in phytoplasma infection response. After infection, syta-1 plants displayed 50% less callose deposition and an uneven distribution pattern of the pathogen. In conclusion, our work shows that SYTA is required for maintaining the unique shape of the SE endomembrane system, and for diverse SE functions including callose deposition, carbon translocation and response to pathogens.

plant biology↗
bioRxiv2026

Combating citrus greening disease by simultaneously targeting the pathogen and callose-mediated phloem occlusion

Huanglongbing (HLB), caused by Candidatus Liberibacter asiaticus (CLas), disrupts sugar transport in citrus due to bacterial proliferation and excessive callose deposition that blocks sieve elements. Unblocking phloem may reduce symptoms, but it is unclear whether targeting CLas or suppressing callose deposition is more critical, as both contribute to phloem dysfunction. This study evaluated whether an integrated strategy targeting both CLas and callose-mediated phloem blockage could more effectively restore phloem transport, carbohydrate allocation, and productivity in HLB-affected citrus. Two complementary field experiments assessed the effects of an antibiotic, a callose inhibitor, and their combination on phloem recovery and source-sink dynamics. The first experiment focused on treatment-induced changes in carbon transport between source and sink shortly after delivery via stem infiltration, capturing immediate physiological responses. The second experiment assessed cumulative carbon allocation to determine sustained effects on assimilate transport and fruit development. Callose inhibitor treatment increased sugar transport but this immediate response did not yield lasting benefits. Antibiotic treatment enhanced carbon import into developing fruits, but these effects were not consistently supported by other physiological indicators. In contrast, the combined treatment reduced callose deposition, improved phloem conductivity and carbon allocation during high sink demand, decreased fruit abscission, and increased the total carbon accumulated in the fruits after physiological fruit drop. Collectively, these results demonstrate that impaired source-sink balance in HLB-affected citrus results from the combination of both pathogen load and host callose accumulation, supporting an integrated strategy that combines pathogen suppression with modulation of host phloem function to improve orchard productivity.

plant biology↗
bioRxiv2025

Tuning Histone Site Selectivity in the Nucleosome with Organometallic Agents

Platinum anticancer drugs tend to target DNA whereas certain ruthenium and osmium organometallic compounds, including those with known anticancer activity, preferentially bind histone proteins in chromatin. We earlier found that Ru/Os arene 2-pyridinecarbothioamide antitumor agents display unique or partially overlapping profiles of histone protein binding in the nucleosome compared to Ru arene phosphaadamantane (RAPTA) antimetastasis drugs, but the basis for this difference is unclear. Here we structurally characterized the nucleosome binding effects of arene ligand substitutions and carried out a multiscale simulation analysis, which reveals that the interplay between metal cation and non-leaving ligand identity dictates adduct stability and whether complexes target electronegative surface patches, internal crevices, or both. We show that the nucleosome superhelical crevice acts as a small molecule selectivity filter and that multi-site binding profiles can be expanded or reduced through defined ligand substitutions, which modulate dynamic and steric attributes. Our findings suggest new avenues for rationally developing Ru/Os organometallics that could help expand the scope of chromatin-targeting therapeutics. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/688318v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@188bc1dorg.highwire.dtl.DTLVardef@1f619d5org.highwire.dtl.DTLVardef@1a0ebaorg.highwire.dtl.DTLVardef@bd0abb_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗
bioRxiv2025

A secreted citrus protease cleaves an outer membrane protein of the Huanglongbing pathogen

Plants secrete a variety of proteases as a defense response during infection by microbial pathogens. However, the relationship between their catalytic activities and antimicrobial functions remains largely unknown. Particularly, few biologically relevant substrates of these proteases have been identified. Huanglongbing (HLB) has been a major threat to the citrus industry worldwide. The HLB-associated bacterium, Candidatus Liberibacter asiaticus (Las), was previously shown to deploy an inhibitor of papain-like cysteine proteases (PLCPs) to promote disease in citrus. In this study, we identified an outer membrane protein (OMP) of Las, LasOMP1, as a substrate of the citrus PLCP CsRD21a. LasOMP1 is one of the most highly expressed genes in Las. CsRD21a cleaves LasOMP1 and produces cleaved peptide products, which could be detected in vitro and in HLB-diseased citrus plants. We found that CsRD21a targets the N-terminal portion of LasOMP1, potentially at an extracellular loop region. Importantly, transgenic sweet orange overexpressing CsRD21a showed reduced Las titers and delayed disease symptoms, highlighting that engineering this protease is a promising strategy to enhance HLB resistance in citrus. Together, our work reveals a pathogen-derived substrate of plant PLCPs and highlights bacterial OMPs as direct targets of plant defense. Significance StatementHuanglongbing (HLB) is the most devastating disease of citrus with no resistance having been identified in commercial cultivars. Previous work implicated papain-like cysteine proteases (PLCPs) as an important hub of defense in citrus; however, their precise role in HLB tolerance remained unclear. Here, we identify and characterize an outer membrane protein (OMP) from the HLB-associated bacterium as a substrate of the citrus PLCP RD21a. We demonstrate a specific cleavage of the bacterial OMP by citrus RD21a, which may impair pathogen growth and/or activate plant immunity. Importantly, overexpression of RD21a enhances HLB tolerance in sweet oranges. This work identifies OMPs as substrates of plant PLCPs and provides insights into protease defense functions.

plant biology↗
bioRxiv2025

Behavioral Decoding Reveals Cortical Endocannabinoid Potentiation during Δ9-THC Impairment

How {Delta}9-tetrahydrocannabinol (THC) impairs natural behaviors in mice remains unknown. We developed a video-monitored behavioral platform with machine learning classifiers to unravel discrete changes in natural mouse behaviors. THC infusion into the medial prefrontal cortex (mPFC) disrupted walking kinematic features characteristic of impairment responses. THC predominantly increased mPFC GABAergic activity preceding walk initiation shifting the mPFC excitatory/inhibitory (E/I) balance. Pose-defined closed loop photo-stimulation of mPFC GABAergic neurons demonstrated that THC exacerbates selected parameters of motor impairment. Surprisingly, THC also induced a time locked, movement-induced, transient potentiation of mPFC endocannabinoid (eCB) release and ensuing CB1R-mediated synaptic inhibition. Here we establish that THC-modifies mPFC E/I balance to excitation via dynamic changes in eCB release which acts to induce behavioral impairment.

neuroscience↗
bioRxiv2025

Unsupervised learning of structural variability in cryo-EM data using normal mode analysis of deformable atomic models

Cryogenic electron microscopy (cryo-EM) has emerged as the method of choice to characterize the structural variability of biomolecules at near-atomic resolution. We present a reconstruction approach that eliminates the need for post-hoc atomic model fitting in 3D maps by deforming a given atomic model along its normal modes directly against the 2D data. This end-to-end approach inherently reduces the risk of error propagation while increasing interpretability of resulting structural ensembles.

biophysics↗
bioRxiv2025

The Genetic Basis of Bacterial Adaptation to Hosts

Microbes colonize and interact with diverse multicellular hosts using specialized genes, many of which remain unidentified. Better understanding of host-associated gene functions is a key aspect of microbial ecology. We utilized a large-scale comparative genomics approach to identify and characterize host-associated functions by comparing 72,079 high-quality bacterial genomes from host and non-host environments using five enrichment tests for high accuracy. We uncovered over 3,000 protein domains, 16,000 AlphaFold protein clusters, and 1,500 operons enriched in host-associated bacteria. Additionally, we identified proteins and domains that are enriched in animal- or plant-associated bacteria. These include new functions such as mercury detoxification in hosts and animals in particular, and numerous proteins and domains of unknown function. We validated our results by genetically disrupting five poorly annotated host-associated genes in plant-associated bacteria, resulting in a substantial reduction in rice root colonization. One of the new colonization factors strongly affected bacterial motility and resistance of oxidative stress. Our findings, presented in a new database, GOTHAM DB, reveal the genetic basis of bacterial host association, including new functions underlying host-microbe interactions, and advance our understanding of microbial evolution.

microbiology↗
bioRxiv2025

How do bacterial extracellular Contractile Injection Systems bind target cells? A remarkable diversity of receptor binding domains

Extracellular contractile injection systems (eCISs) represent a diverse family of bacteriophage tail-derived toxin delivery complexes in prokaryotes. eCISs are vital for microbial interaction with hosts, and they use tail fiber proteins for target cell binding. However, the identity of the tail fiber proteins and their target cells are unknown. Here, we conducted a comprehensive exploration of eCIS tail fiber genes, providing insights into their remarkable diversity, target cells, functional adaptations, and intriguing evolutionary dynamics. We identified 3,445 eCIS tail fiber proteins found in 2,585 eCIS loci from 1,069 microbes. These fibers can be categorized by five new N-terminal domains responsible for tail fiber attachment to eCIS baseplates. Importantly, we leveraged structure prediction to divide the fibers into 276 structural clusters and dissected 1,177 domain fold families which likely mediate glycan and protein binding on the cell surface of eukaryotes or bacterial targets. These rapidly evolving domains are likely acquired from diverse genomes of eukaryotes, bacteria, and viruses. Finally, we experimentally showed that a candidate tail fiber from Paenibacillus eCIS can bind and direct effector injection into THP-1 human monocyte-like cells, and may bind D-mannose on the cell surface. This study reveals the exceptional diversity of eCIS target specificity determinants, suggests new eCIS target cells in Nature, and provides thousands of proteins that adhere to different cell types.

microbiology↗
bioRxiv2025

Simons Sleep Project (SSP): An open science resource for accelerating scalable digital health research in autism and other psychiatric conditions

Wearable and nearable devices offer a novel opportunity to measure extensive behavioral and neurophysiological data directly from participants in their home environment. The Simons Sleep Project (SSP) was designed to accelerate research into sleep and daily behaviors in individuals with autism using such techniques. This open-science resource contains raw and processed data from Dreem3 EEG headbands, multi-sensor EmbracePlus smartwatches, and Withings Sleep mats, as well as parent questionnaires and daily sleep diaries. Data were collected successfully for >3600 days/nights from 102 adolescents (10-17 years old) with idiopathic autism and 98 of their non-autistic siblings. Whole-exome sequencing data is also available for all participants and their parents. To demonstrate the utility of this extensive dataset, we first present the breadth of synchronized high-resolution data available across multiple sensors/devices. We then demonstrate that objective sleep measures (e.g., total sleep time) from the three devices are more accurate and reliable than parent reported measures and reveal that sleep onset latency (SOL) was the only objectively defined sleep measure that differed significantly between autistic children and their siblings (of those examined in the study). Moreover, SOL was reliably associated with the severity of multiple behavioral difficulties in all children, regardless of autism diagnosis. These results highlight the importance of measuring sleep directly from participants using objective measures and demonstrate the extensive opportunities afforded by the SSP to further study autism and develop new digital phenotyping techniques for multiple research domains.

neuroscience↗