Biology subjects

Ou, Y.

Publications and source records attributed to Ou, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Histone modifications define distinct nucleosome positions in cell-free DNA

Circulating cell-free DNA (cfDNA) fragmentation patterns reflect nucleosome positioning. We asked whether variation in nucleosome positions in cfDNA can reveal chromatin states and associated histone modifications. Using cell-free chromatin immunoprecipitation sequencing (cfChIP-seq) in plasma from patients with prostate cancer, we identified 35,120 modification-associated positions (MAPs), loci where nucleosomes bearing active (H3K4me2) and repressive (H3K9me3) histone marks occupy reproducibly offset positions. These offsets recurred across histone marks, an independent cfChIP-seq cohort, and nuclease-digested chromatin from cell lines. MAPs were enriched in transcribed genes but depleted near transcription start sites and CTCF-binding sites where nucleosome positioning is constrained. Across 2,535 cfDNA sequencing datasets, nucleosome protection at a subset of MAPs correlated with tumor fraction (TF), reflecting differences in histone modification status between cancer-derived and non-malignant chromatin. In targeted sequencing panels, a 50-MAP model using fragments from < 0.001% of the genome distinguished samples with tumor fractions [≥]3% vs 0% (AUCs = 0.91-0.96 across prostate, breast, and lung cancers) and outperformed a state-of-the-art fragmentomics-based tumor fraction predictor. MAP-derived estimates correlated with reference TFs (r = 0.89) and longitudinal changes in TF (r = 0.91). MAP protection at ASCL1 binding sites identified neuroendocrine transformation of prostate cancer from cfDNA. These findings establish histone-modification-associated nucleosome positioning as a mutation-independent readout of tumor fraction and cancer state from routine cfDNA sequencing.

cancer biology↗

bioRxiv2026

Xenon improves autism-like behaviors in mice through potentiation of PVT-CeA glutamatergic neurotransmission

Autism spectrum disorder (ASD) is a common neurodevelopmental disease with no currently effective treatments. In this study, Xenon (Xe), a noble gas used clinically as an anesthetic and a neuroprotectant, has been investigated for its potential therapeutic effects in ASD. Two genetic ASD mouse models (Mef2c mutant and Shank3-/- mice) were exposed to a low concentration of xenon (25%) mixed with oxygen (30%) and balanced with nitrogen for a single exposure of 30 min or for 10 min per day for 10 days. These Xe exposure paradigms rescued ASD-like behaviors in both male and female mice. The behavioral improvements persisted for up to 10 days following termination of the 10-day exposure paradigm. Mechanistically, Xe reduced glutamic acid decarboxylase expression in the inhibitory neurons (verified with RNAseq) of the paraventricular thalamic nucleus (PVT) and decreased GABA release during social interaction. Targeted infusion of the GABAA receptor agonist muscimol into the PVT abolished the Xe-mediated behavioral improvements. Reduced GABAergic transmission following Xe exposure increased PVT glutamatergic neuronal activity. Chemogenetic inhibition of these neurons eliminated the therapeutic effects of Xe, whereas chemogenetic activation mimicked the Xe-induced behavioral improvements. Furthermore, opto-inhibition of PVT glutamatergic projections to the central amygdala (CeA) blocked Xe-mediated behavioral improvement. Opto-activation of the PVT-CeA glutamatergic circuit reversed ASD-like behaviors. These findings demonstrate that Xe ameliorates ASD-like phenotypes in mouse models by modulating the PVT Glu-CeA circuit, supporting Xe as a novel potential therapy for ASD.

animal behavior and cognition↗

bioRxiv2026

Unsupervised nonmotor learning in the human cerebellum

A core motor function of the cerebellum is error-based learning: it uses prediction errors--mismatches between predicted and actual sensory feedback--to refine actions. One provocative hypothesis is that the cerebellum performs similar computations in cognitive domains. Here, we ask whether error-based learning computations in the cerebellum extend to a passive statistical learning task that requires neither action nor decision-making. Human participants viewed sequences of visual stimuli with varying probabilistic stimulus-stimulus transitions while undergoing fMRI. Subjects reported no explicit knowledge of the transitional probabilities after the scan. Nonetheless, putative cognitive regions of the cerebellum encoded prediction errors during statistical learning. Moreover, error signals in the cerebellum were encoded in a different manner than error signals in the anterior hippocampus, a well-known substrate of statistical learning: cerebellar activity covaried with trial-by-trial prediction errors that evolved slowly over time (echoing cerebellar computations in motor learning), whereas the hippocampus responded in a more fixed manner to the underlying transition structure. Computational modeling formalized this dissociation, with cerebellar activity explained by a delta-rule model that incrementally adjusted predictions based on recent experience, and hippocampal activity characterized as a form of Bayesian updating of a transition distribution held in memory. Our findings demonstrate that the cerebellum encodes prediction errors during passive nonmotor learning, and thus that it likely plays a domain-general role in error-based learning. SignificanceThe cerebellum is known to support motor learning by using prediction errors to refine behavior. Here, we test whether these computations extend to nonmotor learning contexts that require neither action nor decision-making. We report the discovery of prediction error signals in the cerebellum during statistical learning, an unsupervised process that extracts regularities from the sensory environment. These findings support a domain-general role for the cerebellum in error-based learning, offering a possible explanation for why cerebellar damage is implicated in such wide-ranging outcomes, from impaired motor coordination to complex disorders like autism.

neuroscience↗

bioRxiv2026

Complex coacervation reshapes the aggregation landscape of tau

Biomolecular condensates are increasingly implicated in protein aggregation, yet their contribution is often reduced to that of concentrating reactants. Whether the phase state of a protein itself changes how it aggregates remains unclear. Using complex coacervates of a tau repeat-domain construct (K12) with heparin, we show that phase separation does not simply accelerate tau aggregation but redirects it along a distinct kinetic regime. Amyloid nucleation and growth are largely associated with the condensed phase, where intact phase-separated mixtures nucleate with a markedly shortened lag phase, whereas the corresponding dilute phase contributes little to overall amyloid formation. Aggregation kinetics in this regime become largely decoupled from total protein concentration. Because phase equilibrium pins the composition of the dense phase, additional tau partitions largely into the coexisting dilute phase without substantially altering the reacting population. This weak concentration dependence provides a kinetic signature of compartmentalized aggregation, and it recurs across chemically distinct coacervates formed with heparin, RNA, and polyglutamate, pointing to a general feature of coacervate-mediated tau assembly rather than a heparin-specific effect. Aggregation within coacervates also yields fibrils with altered morphology and secondary structure, suggesting access to alternative regions of the assembly landscape, and shows reduced sensitivity to bulk pH perturbations. Together, these results show that condensation changes tau aggregation by defining the local reaction environment: phase equilibrium buffers the dense-phase composition, in turn altering aggregation kinetics and the properties of the amyloid formed.

biophysics↗

bioRxiv2026

Integrated inference of cancer gene expression from cell-free plasma chromatin

Gene expression is a defining determinant of tumor identity, behavior, and therapeutic response, yet remains challenging to measure noninvasively. Here, we introduce APEX (Associating Plasma Epigenomic features with eXpression), a framework for inferring expression from circulating cell-free chromatin. Trained on [~]270,000 gene-sample pairs from matched tumor RNA-seq and plasma cfChIP-seq across multiple cancers and validated on >15 unseen cancer subtypes, APEX accurately infers cancer gene expression across a range of tumor fractions and outperforms existing plasma-based approaches by integrating positional histone mark and DNA fragmentation patterns across promoters and gene bodies. Using plasma alone, APEX enables classification of prognostically relevant basal and classical pancreatic cancer subtypes and identifies plasma-inferred NECTIN4 expression as a biomarker of response to enfortumab vedotin in metastatic bladder cancer. Together, these findings establish APEX as a biopsy-free approach for profiling tumor transcriptional states and extend liquid biopsy beyond genomic alterations to clinically relevant gene expression programs.

genomics↗

bioRxiv2025

Emergence of hypervirulent Klebsiella pneumoniae ST111 with a novel virulence plasmid causing pyogenic liver abscess

Hypervirulent Klebsiella pneumoniae (hvKp)-associated pyogenic liver abscess is typically linked to K1/K2 capsule serotypes and canonical lineages such as ST23, ST65, and ST86. Cases outside these lineages are rare but pose significant public health concerns. We investigated an unusual liver abscess in an immunocompetent patient caused by hvKp sequence type 111 (ST111). Five isolates (KP1-KP5) were recovered, all belonging to the same clonal lineage. Genomic analysis revealed a 181 kb IncHI1B/IncFIB virulence plasmid encoding rmpADC and the salmochelin cluster (iroBCDN), but lacking aerobactin (iuc) and rmpA2 gene loci. Notably, this plasmid also carried the yersiniabactin locus (ybt), which is typically located on the chromosome. Comparative genomics indicated that similar ST111 strains have been reported only in China, suggesting clonal expansion of a previously unrecognized hvKp lineage. Functional assays demonstrated that plasmid curing abolished the hypermucoviscous phenotype, reduced capsule production, and completely attenuated virulence in murine models, confirming the plasmid as the major driver of hypervirulence. Interestingly, plasmid loss enhanced biofilm formation and relieved growth burden, highlighting fitness trade-offs associated with virulence. This study documents a rare case of hvKp ST111 liver abscess and identifies a novel plasmid conferring hypervirulence. Our findings expand the known diversity of hvKp and underscore that non-canonical lineages can acquire potent virulence determinants enabling severe disease. Continued clinical and genomic surveillance is essential to detect emerging hvKp clones before widespread dissemination.

microbiology↗

bioRxiv2025

Atlas of Breast Cancer in Chinese Young Women Revealed by Single-cell RNA and ATAC Sequencing

Young women with breast cancer (YBC, age[<=]40) are particularly prevalent in Asian. YBCs usually show more aggressive pathology and poorer outcomes than non-young patients. However, YBCs are underrepresented in current BC risk models, with their tumor intrinsic subtypes and microenvironments lacking a systematic elucidation at the single-cell level, thereby limiting the young-specific therapies. We established a single-cell Chinese YBC landscape baseline, including 246,659 cells, by applying scRNA-seq and scATAC-seq on untreated patients. We developed a cross-modal feature selection algorithm to construct a young-intrinsic subtype classifier BCYtype, outperforming existing classifiers in pseudobulk, cellular, and external cohorts. Comparative analyses with non-young samples revealed a direct differentiation trajectory from mammary stem cells to mature luminal cells. Pseudotemporal analysis also demonstrated that tumor cells in younger patients undergo earlier carcinogenesis. Mechanistically, we found that CDH1 interacts with pTex and NKT cells, serving as a young-specific marker and a potential therapeutic target for HR+ young patients. The interaction between exhausted T cells and antigen-presenting cells revealed NKG2A as a candidate therapeutic target for triple-negative breast cancer in young patients.

cancer biology↗

bioRxiv2025

The human cerebellum encodes temporally sensitive reinforcement learning signals

In addition to supervised motor learning, the cerebellum also supports nonmotor forms of learning, including reinforcement learning (RL). Recent studies in animal models have identified core RL signals related to reward processing, reward prediction, and prediction errors in specific regions in cerebellar cortex. However, the constraints on these signals remain poorly understood, particularly in humans. Here, we investigated cerebellar RL signals in a computationally-driven fMRI study. Human participants performed an RL task without low-level sensorimotor contingencies. We observed robust RL signals related to reward processing and reward prediction errors in cognitive regions of the cerebellum (Crus I and II). These signals were not explained by oculomotor or physiological confounds. By manipulating the delay between choices and reward outcomes, we discovered that cerebellar RL signals are temporally sensitive: robust when feedback was delivered shortly following choices, but undetectable at supra-second feedback delays. Similar delay effects were not found in other areas implicated in reward processing, including the ventral striatum and hippocampus. Further, reward prediction error activity in the cerebellum was related to behavioral performance when feedback was delivered promptly, but not when it was delayed. Connectivity analyses revealed that during RL feedback, cognitive areas of the cerebellum coactivate with a network that includes the medial and lateral prefrontal cortex and caudate nucleus. Together, these results highlight a temporally constrained contribution of the human cerebellum to a cognitive learning task.

neuroscience↗

bioRxiv2025

A two-dimensional space of linguistic representations shared across individuals

Our ability to extract meaning from linguistic inputs and package ideas into word sequences is supported by a network of left-hemisphere frontal and temporal brain areas. Despite extensive research, previous attempts to discover differences among these language areas have not revealed clear dissociations or spatial organization. All areas respond similarly during controlled linguistic experiments as well as during naturalistic language comprehension. To search for finer-grained organizational principles of language processing, we applied data-driven decomposition methods to ultra-high-field (7T) fMRI responses from eight participants listening to 200 linguistically diverse sentences. Using a cross-validation procedure that identifies shared structure across individuals, we find that two components successfully generalize across participants, together accounting for about 32% of the explainable variance in brain responses to sentences. The first component corresponds to processing difficulty, and the second--to meaning abstractness; we formally support this interpretation through targeted behavioral experiments and information-theoretic measures. Furthermore, we find that the two components are systematically organized within frontal and temporal language areas, with the meaning-abstractness component more prominent in the temporal regions. These findings reveal an interpretable, low-dimensional, spatially structured representational basis for language processing, and advance our understanding of linguistic representations at a detailed, fine-scale organizational level.

neuroscience↗

bioRxiv2025

AI-driven computational pathology for recurrence risk assessment in early-stage breast cancer

Recurrence related to poor prognosis is a leading cause of mortality in patients with breast cancer (BC). The MammaPrint (MP) genomic assay is designed to stratify recurrence risk and evaluate chemotherapy benefits for early-stage HR+/HER2- BC patients. However, MP fails to reveal spatial tumor morphology and is limited by high costs. In this study, we establish a BC MP cohort and develop CPMP, a weakly supervised agent-attention transformer model, to predict MP recurrence risk from annotation-free BC histopathological slides. CPMP achieves an AUROC of 0.824 {+/-} 0.03 in predicting MP risk groups. We further leveraged CPMP for spatial and morphological analyses to explore histological patterns associated with MP risk groups. The model reveals tumor spatial localization at the whole-slide level and highlights distinct intercellular interaction patterns of MP groups. It also characterizes the diversity in tumor morphology and uncovers MP High-specific, Low-specific, and colocalized morphological phenotypes that differ in quantitative cellular composition. Prognostic evaluation in the external cohort exhibits significant stratification of distant metastasis risk (HR: 3.14, p-value = 0.0014), underscoring the prognostic power of CPMP. These findings demonstrate the capability of CPMP in MP risk prediction, offering a flexible supplement to genomic risk assessment in early-stage BC.

pathology↗

bioRxiv2025

Spatial Prior-Guided Boundary and Region-Aware 2D Lesion Segmentation in Neonatal Hypoxic Ischemic Encephalopathy

Segmenting acute and hyper-acute brain lesions in neona-tal hypoxic-ischemic encephalopathy (HIE) from diffusion-weighted MRI (DWI) is critical for prognosis and treatment planning but remains challenging due to severe class imbalance and lesion variability. We propose a computationally efficient 2D segmentation framework leveraging ADC and ZADC maps as a three-channel input to UNet++ with an Inception-v4 encoder and scSE attention for enhanced spatial-channel recalibration. To address class critical imbalance and lack of volumetric context in 2D methods, we introduce a novel boundary-and-region-aware weighted loss integrating Tversky, Log-Hausdorff, and Focal losses. Our method surpasses state-of-the-art 2D approaches and achieves competitive performance against computationally intensive 3D architectures, securing a Dice Similarity Coefficient (DSC) of 0.6060, Mean Average Surface Distance (MASD) of 2.6484, and Normalized Surface Distance (NSD) of 0.7477. These results establish a new benchmark for neonatal HIE lesion segmentation, demonstrating superior detection of both acute and hyper-acute lesions while mitigating the challenge of loss collapse. The code is available at Neonatal-HIE-SPARSeg.

bioinformatics↗

bioRxiv2025

Cortical substrates of perceptual confusion between pitch and timbre

Pitch and timbre, two fundamental perceptual attributes of sound, are critical for both speech and music. Although governed by different acoustic parameters, pitch and brightness (one of the primary dimensions of timbre) can be perceptually confused. Here we identify potential neural substrates of this well-known illusion by independently manipulating pitch and brightness while measuring fMRI responses. First, we show that the preferred pitch of individual voxels within auditory cortex decreases systematically as stimulus brightness increases, and vice versa, consistent with predictions from perceptual confusion. Second, we demonstrate that pitch and brightness share a common tuning gradient across auditory cortex, implying a shared trajectory of cortical activation for changes in each dimension. The pattern of results at both local and global cortical levels are consistent with the principle of efficient coding, with the brain exploiting correlations between pitch and brightness in natural sounds via a shared neural code.

neuroscience↗

bioRxiv2024

Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes anteriorly past the left. Here, we ask whether neuroanatomical asymmetries can be observed in mice, leveraging 6 mouse neuroimaging cohorts from 5 different research groups ([~]3,500 animals). We found an anterior-posterior pattern of volume asymmetry with anterior regions larger on the right and posterior regions larger on the left. This pattern appears driven by similar trends in surface area and positional asymmetries, with the results together indicating a small brain-wide twisting pattern, similar to the human cerebral petalia. Furthermore, the results show no apparent relationship to known functional asymmetries in mice, emphasizing the complexity of the structure-function relationship in brain asymmetry. By establishing a signature of anatomical brain asymmetry in mice, we aim to provide a foundation for future studies to probe the mechanistic underpinnings of brain asymmetry seen in humans - a feature of the brain with extremely limited understanding. Significance StatementThe human brain shows significant left-right anatomical asymmetry. Understanding its microscopic basis has implications for studies of autism and schizophrenia, evolution, embryonic brain development, and the relationship between structure and function in the brain. One of the biggest challenges to understanding this aspect of the brain is that animal models are limited. Here we show a brain-wide twisting pattern of asymmetry in the mouse brain using over 3,500 animals from six independent cohorts. These findings provide a basis for using mice to interrogate the microscopic underpinnings of anatomical asymmetry in humans and a roadmap for exploring anatomical asymmetry in additional species.

neuroscience↗

bioRxiv2024

Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration

During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here we analyzed the role of microglia in the synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to ameboid morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially restores ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting their recruitment to synaptic sites early after neuronal injury. HighlightsEarly after transient intraocular pressure elevation: O_LIMicroglia increase in number, complexity, and process movement C_LIO_LIMicroglia-synaptic contacts increase in the inner plexiform layer C_LIO_LIMicroglia-synaptic contacts increase on retinal ganglion cell dendrites C_LIO_LIMicroglia depletion partially restores ganglion cell function C_LI

neuroscience↗

bioRxiv2024

Compromised actin dynamics underlie the orofacial cleft in Baraitser-Winter Cerebrofrontofacial Syndrome with a variant in ACTB

Craniofacial anomalies encompassing the orofacial cleft are associated with >30% of systemic congenital malformations. Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF) is a rare genetic disorder attributed to variants in the actin beta (ACTB) or actin gamma genes that are correlated with a range of craniofacial abnormalities, including cleft lip and/or palate. The underlying pathological mechanism of BWCFF remains elusive, and it is necessary to investigate the etiology of orofacial clefts in BWCFF. In this study, we identified a missense variant (c.1043C>T: p.S348L) in the ACTB gene from a patient with BWCFF and concomitant cleft lip and palate. Furthermore, we performed functional assessments of this variant using various disease models such as the MDCK cell line and Xenopus laevis. These models revealed a compromised capacity of mutated ACTB to localize at the epithelial junction, consequently affecting the behavior of epithelial cells. Additionally, we made the noteworthy discovery that mutated ACTB exhibited an impaired ability to bind PROFILIN1, a critical factor in actin polymerization. This defective ability may contribute to the molecular etiology of aberrant epithelial cell adhesion and migration, resulting in orofacial cleft formation in BWCFF. Author SummaryAdvances in clinical sequencing have rapidly elucidated the genetic basis of rare diseases affecting multiple organs. In this study, we investigate the role of a variant in the ACTB gene, which is fundamental to cell structure, in causing orofacial clefts in the Baraitser-Winter Cerebrofrontofacial Syndrome (BWCFF), known for its distinctive facial anomalies. Using epithelial cell lines and frog embryo models, we investigated the effects of the ACTB gene alteration on cellular functions. Our results indicate that this genetic change disrupts the normal adhesion and movement of epithelial cells, processes that are critical for facial development. This research underscores the importance of the ACTB gene in shaping the face and suggests new directions for future research, potentially informing the diagnosis and treatment of BWCFF and related conditions.

genetics↗

bioRxiv2024

Biallelic pathogenic variants in DNAH3 cause male infertility in humans and mice

Axonemal protein complexes, including the outer and inner dynein arms (ODA/IDA), are highly ordered structures of the sperm flagella that drive sperm motility. Deficiencies in several axonemal proteins have been associated with male infertility, which is characterized by asthenozoospermia or asthenoteratozoospermia. Dynein axonemal heavy chain 3 (DNAH3) resides in the IDA and is highly expressed in the testis. However, the relationship between DNAH3 and male infertility is still unclear. Herein, we identified biallelic variants of DNAH3 in four unrelated Han Chinese infertile men with asthenoteratozoospermia through whole-exome sequencing (WES). These variants contributed to deficient DNAH3 expression in the patients sperm flagella. Importantly, the patients represented the anomalous sperm flagellar morphology, and the flagellar ultrastructure was severely disrupted. Intriguingly, Dnah3 knockout (KO) male mice were also infertile, especially showing the severe reduction in sperm movement with the abnormal IDA and mitochondrion structure. Mechanically, nonfunctional DNAH3 expression resulted in decreased expression of IDA-associated proteins in the spermatozoa flagella of patients and KO mice, including DNAH1, DNAH6, and DNALI1, the deletion of which has been involved in disruption of sperm motility. Moreover, the infertility of patients with DNAH3 variants and Dnah3 KO mice could be rescued by intracytoplasmic sperm injection (ICSI) treatment. Our findings indicated that DNAH3 is a novel pathogenic gene for asthenoteratozoospermia and may further contribute to the diagnosis, genetic counseling, and prognosis of male infertility.

genetics↗

bioRxiv2024

SOX9-regulated matrix proteins predict poor outcomes in patients with COVID-19 and pulmonary fibrosis

Pulmonary fibrosis is an increasing and major cause of death worldwide. Understanding the cellular and molecular mechanisms underlying the pathophysiology of lung fibrosis may lead to urgently needed diagnostic and prognostic strategies for the disease. SOX9 is a core transcription factor that has been associated with fibrotic disease, however its role and regulation in acute lung injury and/or fibrosis have not been fully defined. In this study we apply a hypothesis based approach to uncover unique SOX9-protein signatures associated with both acute lung injury and fibrotic progression. Using in vivo models of lung injury in the presence or absence of SOX9, our study shows SOX9 is essential to the damage associated response of alveolar epithelial cells from an early time-point in lung injury. In parallel, as disease progresses, SOX9 is responsible for regulating tissue damaging ECM production from pro-fibrotic fibroblasts. In determining the in vivo role of SOX9 we identified secreted ECM components downstream of SOX9 as markers of acute lung injury and fibrosis. To underscore the translational potential of our SOX9-regulated markers, we analysed serum samples from acute COVID19, post COVID19 and idiopathic pulmonary fibrosis (IPF) patient cohorts. Our hypothesis driven SOX9-panels showed significant capability in all cohorts at identifying patients who had poor disease outcomes. This study shows that SOX9 is functionally critical to disease in acute lung injury and pulmonary fibrosis and its regulated pathways have diagnostic, prognostic and therapeutic potential in both COVID19 and IPF disease.

molecular biology↗

bioRxiv2023

Enhancing Neurocognitive Outcome Prediction in Congenital Heart Disease Patients: The Role of Brain Age Biomarkers and Beyond

This paper aimed to investigate the predictive power of combining demographic, socioeconomic, and genetic factors with a brain MRI-based quantified measure of accelerated brain aging (referred to as deltaAGE) for neurocognitive outcomes in adolescents and young adults with Congenital Heart Disease (CHD). Our hypothesis posited that including the brain age biomarker (deltaAGE) would enhance neurocognitive outcome predictions compared to models excluding it. We conducted comprehensive analyses, including leave-one-subject-out and leave-one-group-out cross-validation techniques. Our results demonstrated that the inclusion of deltaAGE consistently improved prediction performance when considering the Pearson correlation coefficient, a preferable metric for this study. Notably, the deltaAGE -augmented models consistently outperformed those without deltaAGE across all cross-validation setups, and these correlations were statistically significant (p-value < 0.05). Therefore, our hypothesis that incorporating the brain-age biomarker alongside demographic, socioeconomic, and genetic factors enhances neurocognitive outcome predictions in adolescents and young adults with CHD is supported by the findings.

bioinformatics↗