Biology subjects

Sun, P.

Publications and source records attributed to Sun, P..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

Herb-paths, a network and statistical model to explore health-beneficial effects of herbs and herbal constituents

Predictions on bioactivities of herbs and herbal compounds could greatly aid drug development, but require integration of available information on herb and compound effects from various databases. We present Herb-paths, an integrated network connecting information on health-beneficial effects of herbs and herbal constituents. The statistical models included in Herb-paths allow for the calculation of the association strength of herbal (constituents) with health-beneficial effects, for both known and novel effects, and give insight into the major bioactive compounds and molecular mechanisms driving the effects. Herb-paths predictions were tested and validated using a case-study of Panax notoginseng and its derived medicinal extract of Panaxatriol saponins (PTS), used in traditional Chinese medicine to treat stroke and other cardiovascular and cerebrovascular thromboembolic (CCT) disorders. Results showed that Herb-paths predicted known and novel associations between PTS/Notoginseng and CCT phenotypes and diseases, including stroke. Predicted novel associations, such as MoyaMoya disease, are promising putative leads for treatment with PTS/Notoginseng, to be tested in further studies.

bioinformatics↗

bioRxiv2022

Molecular and genetic mechanisms conferring dissolution of dioecy in Diospyros oleifera Cheng

Dioecy, a sexual system of single-sex (gynoecious/androecious) individuals, is rare in flowering plants. This rarity may be a result of the frequent transition from dioecy into systems with co-sex individuals. Here, we report potential molecular and genetic mechanisms that underlie the dissolution of dioecy to monoecy and andro(gyno)monoecy, based on multiscale genome-wide investigations of 150 accessions of Diospyros oleifera. All co-sex D. oleifera plants, including monoecious and andro(gyno)monoecious individuals, possessed the male determinant gene OGI, implying that genetic factors control gynoecia development in genetically male D. oleifera. In both single- and co-sex plants, female function was expressed in the presence of a genome-wide decrease in methylation levels, along with sexually distinct regulatory networks of smRNAs and their targets. Furthermore, a genome-wide association study (GWAS) identified a genomic region and a DUF247 gene cluster strongly associated with the monoecious phenotype, as well as several regions that may contribute to andromonoecy. Collectively, our findings imply stable breakdown of the dioecious system in D. oleifera, presumably a result of the genomic features of the sex-linked region.

plant biology↗

bioRxiv2022

Curation of the Deep Green list of unannotated green lineage proteins to enable structural and functional characterization

An explosion of sequenced genomes and predicted proteomes enabled by low cost deep sequencing has revolutionized biology. Unfortunately, protein functional annotation is more complex, and has not kept pace with the sequencing revolution. We identified unannotated proteins in three model organisms representing distinct parts of the green lineage (Viridiplantae); Arabidopsis thaliana (dicot), Setaria viridis (monocot), and Chlamydomonas reinhardtii (Chlorophyte alga). Using similarity searching we found the subset of unannotated proteins that were conserved between these species and defined them as Deep Green proteins. Informatic, genomic, and structural predictions were leveraged to begin inferring functional information about Deep Green genes and proteins. The Deep Green set was enriched for proteins with predicted chloroplast targeting signals that are predictive of photosynthetic or plastid functions. Strikingly, structural predictions using AlphaFold and comparisons to known structures show that a significant proportion of Deep Green proteins may possess novel protein tertiary structures. The Deep Green genes and proteins provide a starting resource of high value targets for further investigation of potentially new protein structures and functions that are conserved in the green lineage.

plant biology↗

bioRxiv2022

Function of cell adhesion molecules in differentiation of ray sensory neurons in C. elegans.

For proper functioning of the nervous system, it is crucial that neurons find their appropriate partners and build the correct neural connection patterns. Although cell adhesion molecules (CAMs) have been studied for many years as essential players in neural connections, we have yet to unravel the code by which CAMs encode synaptic specificity. We analyzed the effects of mutations in CAM genes on the morphology and synapses of a set of sensory neurons in the C. elegans male tail. B-type ray sensory neurons express ten genes encoding CAMs. We examined the effect on axon trajectory and localization of presynaptic components in viable mutants of nine of these. We found axon trajectory defects in mutants of UNC-40/DCC, SAX-3/ROBO, and FMI-1/Flamingo/Celsr1. In none of the mutants was presence of presynaptic components in axons lost, and in several the level appeared to increase, suggesting possible accumulation. B-type sensory neurons fasciculate with a second type of ray sensory neuron, the A-type, in axon commissures. We found cell non-autonomous effects consistent with each promoting the trajectory of the other. Overall, single and multiple mutants of CAM genes had limited effects on ray neuron trajectories and accumulation of synaptic components.

genetics↗

bioRxiv2022

The Chromosome-level Genome of Dracaena cochinchinesis Provides Insights into its Biological Features and the Mechanism of Dragon's Blood Formation

Dracaena, a remarkably long-lived and slowly maturing species, is famous all over the world for the production of dragons blood, a precious traditional medicine used by different cultures since ancient times. However, lacking a high-quality genome,the molecular mechanisms underlying these traits are largely unknown and that greatly restricts the protection and regeneration of the rare and endangered plant resources. Here, we sequenced and assembled a chromosome-level genome of the Dracaena cochinchinensis, the first to be sequenced of Dracaena Vand. ex L. The D. cochinchinensis genome covering 1.21 Gb with a scaffold N50 of 50.06 Mb, and encodes 31,619 predicted protein-coding genes. We found D. cochinchinensis has undergone two whole genome duplications (WGDs) and two long terminal repeats (LTRs) insertion burst events. The expansion of cis-zeatin O-glucosyltransferase (cZOGT) and small auxin up-regulated RNA (SAUR) genes is account for its longevity and slow growth. In flavonoids biosynthesis pathway, transcription factors bHLH and MYB were predicted as the core regulators, and ROS as the specific signal molecule during the process of injury-induced dragons blood formation. Our study not only provides high-quality genomic knowledge of D. cochinchinensis, but also deciphered the mystery of its longevity, and preliminarily elucidated the molecular mechanism of dragons blood formation, which will facilitate the resource protection and sustainable utilization of Dracaena. SHORT SUMMARYThis study reports a chromosome-level genome assembly for D. cochinchinensis, the first genome of Dracaena Vand. ex L. It 29 provides valuable genetic resources and creates a large scope for studying Dracaena. We found the significant expansion of genes associated with its longevity and slow growth, and genes in flavonoids biosynthesis were first completely identified. Moreover, transcription factors bHLH and MYB as the core regulator of flavonoids biosynthesis, and ROS as the specific signal molecule during the process of injury-induced dragons blood formation were also identified. These results not only deciphered the mystery of its longevity, but also elucidated the molecular mechanism of dragon[s blood formation preliminarily, which will facilitate the resource protection and sustainable utilization of Dracaena.

genomics↗

bioRxiv2022

Transcriptome Analysis of the Nematode Caenorhabditis elegans and Litoditis marina in a Chemically Defined Food Environment

Diets regulate animal development, reproduction, and lifespan. However, the underlying molecular mechanisms remain elusive. A chemically defined CeMM diet attenuates development and promotes longevity of C. elegans, but whether it impact on other nematodes is unknown. Here, we studied the effect of the CeMM diet on the development and longevity of the marine nematode Litoditis marina, which belongs to the same family as C. elegans. We further investigated genome-wide transcriptional responses to CeMM and OP50 diet for both nematodes, respectively. We observed that the CeMM diet attenuated L. marina development but did not extend its lifespan. We found that many of the FOXO DAF-16 target genes, lysosome and xenobiotic metabolism related genes were significantly increased on the CeMM, which might contribute to the lifespan extension of C. elegans. Notably, we found that the expression of lysosome and xenobiotic metabolism pathway genes was significantly down regulated in L. marina on CeMM, which might explain why the CeMM diet could not promote the lifespan of L. marina compared to bacterial feeding. Additionally, down-regulation of several RNA transcription and protein generation and related processes genes might not only be involved in extending longevity but also contribute to attenuating development of C. elegans on CeMM, while down-regulation of unsaturated fatty acids synthesis genes might contribute to slow down the growth of L. marina on CeMM. Further genetic analysis of candidate gene(s) of longevity and development in C. elegans and L. marina will provide the molecular mechanisms underlying how diets regulate animal physiology and health in the context of global climate change with variable nutritional environments.

zoology↗

bioRxiv2021

Contrasting effects of accumulation and tolerance characteristics in Arabidopsis thaliana under Cr(III) and Cr(VI) stress

In this study, for the first time we investigated Cr(III) and Cr(VI) stress-induced physiological and biochemical responses in Arabidopsis thaliana. The capacity of A. thalian to accumulate Cr is closely related to the valence of chromium. Cr(VI) was more toxic than Cr(III) as indicated by chromium accumulation and growth inhibition. When the concentration of chromium is greater than 200M, the root length and biomass of A. thaliana are reduced. But interestingly, Cr(III) at 200M increased the root length and biomass of A. thaliana compared to the control. The transmission electron microscope shows that Cr(VI) can cause the chloroplasts damaged and the chlorophyll reduced more than Cr(III). The chloroplasts were filled the starch grains. An increase of lipid peroxidation in A. thaliana roots caused by Cr was measured, and this effect increases as the increasing Cr. It indicated that A. thaliana suffers from Cr-induced oxidative stress which resulted cell death in roots. To fight against oxidative stress, Ascorbate peroxidase and Glutathione reductase were activated by Cr in antioxidant defense. The inhibition of growth, the accumulation of chromium, the responses of antioxidant systems, and the ultra-morphological changes indicate that Cr(VI) was more toxic than Cr(III).

biochemistry↗

bioRxiv2021

CHARM: COVID-19 Health Action Response for Marines - association of antigen-specific interferon-gamma and IL2 responses with asymptomatic and symptomatic infections after a positive qPCR SARS-CoV-2 test

SARS-CoV-2 T cell responses are associated with COVID-19 recovery, and Class I- and Class II-restricted epitopes have been identified in the spike (S), nucleocapsid (N) and membrane (M) proteins and others. This prospective COVID-19 Health Action Response for Marines (CHARM) study enabled assessment of T cell responses in symptomatic and asymptomatic SARS-CoV-2 infected participants. At enrollment all participants were negative by qPCR; follow-up occurred biweekly and then bimonthly for the next 6 weeks. Study participants who tested positive by qPCR SARS-CoV-2 test were asked to enroll in an immune response sub-study. FluoroSpot interferon-gamma (IFN-{gamma}) and IL2 responses following qPCR-confirmed infection at enrollment (day 0), day 7 and 14 and more than 28 days later were measured using pools of 17mer peptides covering S, N, and M proteins, or CD4+CD8 peptide pools containing predicted epitopes from multiple SARS-CoV-2 antigens. Among 124 asymptomatic and 105 symptomatic participants, SARS-CoV-2 infection generated IFN-{gamma} responses to the S, N and M proteins that persisted longer in asymptomatic cases. IFN-{gamma} responses were significantly (p=0.001) more frequent to the N pool (51.4%) than the M pool (18.9%) among asymptomatic subjects; however, the difference was not statistically significant (p=0.06) for symptomatic subjects (N pool: 44.4%; M pool: 25.9%). In asymptomatic participants IFN-{gamma} responders to the CD4+CD8 pool responded more frequently to the S pool (55.6%) and N pool (57.1%), than the M pool (7.1%), but symptomatic participants, IFN-{gamma} responses were more frequent to the S pool (75.0%) than N pool (33.3%) and M pool (33.3%). The frequencies of IFN-{gamma} responses to the S and N+M pools peaked 7 days after the positive qPCR test among asymptomatic (S pool: 22.2%; N+M pool: 28.7%) and symptomatic (S pool: 15.3%; N+M pool 21.9%) participants and dropped by >28 days. Magnitudes of post-infection IFN-{gamma} and IL2 responses to the N+M pool were significantly correlated with IFN-{gamma} and IL2 responses to the N and M pools. These data further support the central role of Th1-biased cell mediated immunity IFN-{gamma} and IL2 responses, particularly to the N protein, in controlling COVID-19 symptoms, and justify T cell-based COVID-19 vaccines that include the N and S proteins.

immunology↗

bioRxiv2021

Epidermal Growth Factor Receptor Inhibition Prevents Caveolin-1-dependent Calcifying Extracellular Vesicle Biogenesis

Chronic kidney disease (CKD) increases the risk of cardiovascular disease, including vascular calcification, leading to higher mortality. Release of calcifying extracellular vesicles (EVs) by vascular smooth muscle cells (VSMCs) promotes the ectopic mineralization of vessel walls. Caveolin-1 (CAV1) protein plays a key role in genesis of calcifying EVs in VSMCs. Epidermal growth factor receptor (EGFR) co-localizes with and influences the intracellular trafficking of CAV1. Using a diet-induced mouse model of CKD, we measured serum EGFR and assessed the potential of EGFR inhibition to prevent vascular calcification. Mice with CKD developed widespread vascular calcification, which associated with increased serum levels of EGFR. We computationally analyzed 7651 individuals in the Multi-Ethnic Study of Atherosclerosis (MESA) and Framingham cohorts to assess potential correlations between coronary artery calcium and single nucleotide polymorphisms (SNPs) associated with elevated serum levels of EGFR. Individuals in the MESA and Framingham cohorts with SNPs associated with increased serum EGFR exhibit elevated coronary artery calcium. In both the CKD mice and human VSMC culture, EGFR inhibition significantly reduced vascular calcification by mitigating the release of CAV1-positive calcifying EVs. EGFR inhibition also increased bone mineral density in CKD mice. Given that EGFR inhibitors exhibit clinical safety and efficacy in other pathologies, the current data suggest that EGFR may be an ideal target to prevent pathological vascular calcification.

pathology↗

bioRxiv2021

Protein-Metabolite Interactomics Reveals Novel Regulation of Carbohydrate Metabolism

Metabolism is highly interconnected and also has profound effects on other cellular processes. However, the interactions between metabolites and proteins that mediate this connectivity are frequently low affinity and difficult to discover, hampering our understanding of this important area of cellular biochemistry. Therefore, we developed the MIDAS platform, which can identify protein-metabolite interactions with great sensitivity. We analyzed 33 enzymes from central carbon metabolism and identified 830 protein-metabolite interactions that were mostly novel, but also included known regulators, substrates, products and their analogs. We validated previously unknown interactions, including two atomic-resolution structures of novel protein-metabolite complexes. We also found that both ATP and long-chain fatty acyl-CoAs inhibit lactate dehydrogenase A (LDHA), but not LDHB, at physiological concentrations in vitro. Treating cells with long-chain fatty acids caused a loss of pyruvate/lactate interconversion, but only in cells reliant on LDHA. We propose that these regulatory mechanisms are part of the metabolic connectivity that enables survival in an ever-changing nutrient environment, and that MIDAS enables a broader and deeper understanding of that network.

biochemistry↗

bioRxiv2021

Pancreatic Brsk2 amplifies parasympathetic signals to promote type 2 diabetes

The parasympathetic nervous system (PNS) modulates postprandial glucose metabolism via innervating pancreas; however, its significance in the pathogenesis of type 2 diabetes (T2DM) remains unclear. Here we show that brain-specific serine/threonine-protein kinase 2 (Brsk2), accumulated in obese mouse islets, responds to PNS activation and initiates pre-absorptive insulin release. In inducible mouse models, excessive Brsk2 amplifies parasympathetic signaling to {beta} cells and increases their secretion, ensuing insulin resistance and T2DM. Conversely, Brsk2 inhibition prevents and treats HFD-induced metabolic abnormities via avoiding {beta}-cell oversecretion. Mechanistically, parasympathetic acetylcholine activates cholinergic receptor M3 (Chrm3), then Chrm3 recruits and stabilizes Brsk2, which in turn phosphorylates phospholipase A2 activating protein (Plaa). A Chrm3-Brsk2-Plaa axis stimulates {beta}-cell hypersecretion during both pre-absorptive and absorptive stages in HFD-feeding mice, thus imposing insulin resistance and {beta}-cell dysfunction. Blocking parasympathetic signaling to {beta} cells by Brsk2 protein restoration, autonomic mediation drugs, or vagotomy restricted diabetes development. Moreover, three human BRSK2 variants are associated with hyperinsulinemia, insulin resistance, and T2DM in the Chinese population. These findings reveal that Brsk2 links parasympathetic nervous system to nutrition-overload induced T2DM.

pathology↗

bioRxiv2021

WGDI: A user-friendly toolkit for evolutionary analyses of whole-genome duplications and ancestral karyotypes

Evidence of whole-genome duplications (WGDs) and subsequent karyotype changes has been detected in most major lineages of life on Earth. To clarify the complex resulting multiple-layered patterns of gene collinearity in genome analyses there is a need for convenient and accurate toolkits. To meet this need, we introduce here WGDI (Whole-Genome Duplication Integrated analysis), a Python-based command-line tool that facilitates comprehensive analysis of recursive polyploidizations and cross-species genome alignments. WGDI supports three main workflows (polyploid inference, hierarchical inference of genomic homology, and ancestral chromosomal karyotyping) that can improve detection of WGD and characterization of related events. It incorporates a more sensitive and accurate collinearity detection algorithm than previous softwares, and can accelerate WGD-related karyotype research. As a freely available toolkit at GitHub (https://github.com/SunPengChuan/wgdi), WGDI outperforms similar tools in terms of efficiency, flexibility and scalability. In an illustrative example of its application, WGDI convincingly clarified karyotype evolution in Aquilegia coerulea and Vitis vinifera following WGDs and rejected the hypothesis that Aquilegia contributed as a parental lineage to the allopolyploid origin of core dicots.

bioinformatics↗

bioRxiv2021

Deep neural network analysis employing diffusion basis spectrum imaging metrics as classifiers improves prostate cancer detection and grading

Structural and cellular complexity of prostatic histopathology limits the accuracy of noninvasive detection and grading of prostate cancer (PCa). We addressed this limitation by employing a novel diffusion basis spectrum imaging (DBSI) to derive structurally-specific diffusion fingerprints reflecting various underlying prostatic structural and cellular components. We further developed diffusion histology imaging (DHI) by combining DBSI-derived structural fingerprints with a deep neural network (DNN) algorithm to more accurately classify different histopathological features and predict tumor grade in PCa. We examined 243 patients suspected with PCa using in vivo DBSI. The in vivo DBSI-derived diffusion metrics detected coexisting prostatic pathologies distinguishing inflammation, PCa, and benign prostatic hyperplasia. DHI distinguished PCa from benign peripheral and transition zone tissues with over 95% sensitivity and specificity. DHI also demonstrated over 90% sensitivity and specificity for Gleason score noninvasively. We present DHI as a novel diagnostic tool capable of noninvasive detection and grading of PCa. One sentence summaryDiffusion histology imaging noninvasively and accurately detects and grades prostate cancer.

bioinformatics↗

bioRxiv2021

Copy number variation profile-based genomic subtyping of premenstrual dysphoric disorder in Chinese

Premenstrual dysphoric disorder (PMDD) affects nearly 5% women of reproductive age. The symptomatic heterogeneity, along with largely unknown genetics, of PMDD have greatly hindered its effective treatment. In the present study, 127 Chinese PMDD patients of the invasion and depression subtypes clinically differentiated by us earlier were analyzed together with 108 non-PMDD controls for genome-wide copy number variations (CNVs). Germline genomic DNA samples from white blood cells were subjected to AluScan sequencing-based CNV profiling, which enabled clustering of patient samples readily into the V and D groups, dominated by the "invasion" and "depression" clinical subtypes, respectively; the CNVs obtained with 100-kb windows yielded two clusters that were correlated with these subtypes with a consistency of up to 89.8%. Diagnostic correlation- and frequency-based CNV features of either CNV-gain (CNVG) or CNV-loss (CNVL) that could differentiate between V and D subtypes were selected and analyzed. CNVG features located preferentially in S2-phase replicating regions and enriched with steroid hormone biosynthesis pathway of genes were found protective against PMDD. Moreover, machine learning employing the correlation-based CNV features could predict with >80% accuracy whether a genomic sample was D-type, V-type or control. In terms of their CNV profiles, the D- and V-types differed more from one another than from the controls, thereby providing a genomic basis for the clinical D-V subtyping of PMDD. Genome-wide profiling of CNVs, as a new approach to complex disease genetics, has revealed recurrent CNVs and genomic features beyond individual genes and mutations underlying PMDD clinical diversity.

genomics↗

bioRxiv2020

Information Confusion Reveals an Innate Limit of the Information Processing by Neurons

Information experiences complex transformation processes in the brain, involving various errors. A daunting and critical challenge in neuroscience is to understand the origin of these errors and their effects on neural information processing. While previous efforts have made substantial progresses in studying the information errors in bounded, unreliable and noisy transformation cases, it still remains elusive whether the neural system is inherently error-free under an ideal and noise-free condition. This work brings the controversy to an end with a negative answer. We propose a novel neural information confusion theory, indicating the widespread presence of information confusion phenomenon after the end of transmission process, which originates from innate neuron characteristics rather than external noises. Then, we reformulate the definition of zero-error capacity under the context of neuroscience, presenting an optimal upper bound of the zero-error transformation rates determined by the tuning properties of neurons. By applying this theory to neural coding analysis, we unveil the multi-dimensional impacts of information confusion on neural coding. Although it reduces the variability of neural responses and limits mutual information, it controls the stimulus-irrelevant neural activities and improves the interpretability of neural responses based on stimuli. Together, the present study discovers an inherent and ubiquitous precision limitation of neural information transformation, which shapes the coding process by neural ensembles. These discoveries reveal that the neural system is intrinsically error-prone in information processing even in the most ideal cases. Author summaryOne of the most central challenges in neuroscience is to understand the information processing capacity of the neural system. Decades of efforts have identified various errors in nonideal neural information processing cases, indicating that the neural system is not optimal in information processing because of the widespread presences of external noises and limitations. These incredible progresses, however, can not address the problem about whether the neural system is essentially error-free and optimal under ideal information processing conditions, leading to extensive controversies in neuroscience. Our work brings this well-known controversy to an end with a negative answer. We demonstrate that the neural system is intrinsically error-prone in information processing even in the most ideal cases, challenging the conventional ideas about the superior neural information processing capacity. We further indicate that the neural coding process is shaped by this innate limit, revealing how the characteristics of neural information functions and further cognitive functions are determined by the inherent limitation of the neural system.

neuroscience↗

bioRxiv2020

Genome-wide association study reveals the genetic architecture of 27 yield-related traits in tomato

Tomato (Solanum lycopersicum) is a highly valuable vegetable crop and yield is one of the most important traits. Uncovering the genetic architecture of yield-related traits in tomato is critical for the management of vegetative and reproductive development, thereby enhancing yield. Here we perform a comprehensive genome-wide association study for 27 yield-related traits in tomato. A total of 239 significant associations corresponding to 129 loci, harboring many reported and novel genes related to vegetative and reproductive development, were identified, and these loci explained an average of [~]8.8% of the phenotypic variance. A total of 51 loci associated with 25 traits have been under selection, especially during tomato improvement. Furthermore, a candidate gene, SlALMT15 that encodes an aluminum-activated malate transporter, was functionally characterized and shown to act as a pivotal regulator of leaf stomata formation through increasing photosynthesis and drought resistance. This study provides valuable information for tomato genetic research and breeding.

plant biology↗

bioRxiv2020

Structure and allosteric regulation of human IDH3 holoenzyme

Human NAD-dependent isocitrate dehydrogenase or IDH3 catalyzes the decarboxylation of isocitrate into -ketoglutarate in the TCA cycle. We here report the structure of the IDH3 holoenzyme, in which the {beta} and {gamma} heterodimers assemble the 2{beta}{gamma} heterotetramer via their clasp domains, and two 2{beta}{gamma} heterotetramers assemble the (2{beta}{gamma})2 heterooctamer via the {beta} and {gamma} subunits. The functional roles of the key residues involved in the assembly and allosteric regulation are validated by mutagenesis and kinetic studies. The allosteric site plays an important role but the pseudo allosteric site plays no role in the allosteric activation; the activation signal from the allosteric site is transmitted to the active sites of both heterodimers via the clasp domains; and the N-terminus of the {gamma} subunit plays a critical role in the formation and function of the holoenzyme. These findings reveal the molecular mechanism of the assembly and allosteric regulation of human IDH3 holoenzyme.

biochemistry↗

bioRxiv2020

Diffusion Basis Spectrum Imaging with Deep Neural Network Differentiates Distinct Histology in Pediatric Brain Tumors

High-grade pediatric brain tumors constitute the highest mortality of cancer-death in children. While conventional MRI has been widely adopted for examining pediatric high-grade brain tumor clinically, accurate neuroimaging detection and differentiation of tumor histopathology for improved diagnosis, surgical planning, and treatment evaluation, remains an unmet need in the clinical management of pediatric brain tumor. We employed a novel Diffusion Histology Imaging (DHI) approach that incorporates diffusion basis spectrum imaging (DBSI) and deep neural network. DHI aims to detect, differentiate, and quantify heterogenous areas in pediatric high-grade brain tumors, which include normal white matter (WM), densely cellular tumor (DC tumor), less densely cellular tumor (LDC tumor), infiltrating edge, necrosis, and hemorrhage. Distinct diffusion metric combination would thus indicate the unique distributions of each distinct tumor histology features. DHI, by incorporating DBSI metrics and the deep neural network algorithm, classified pediatric tumor histology with an overall accuracy of 83.3%. Receiver operating analysis (ROC) analysis suggested DHIs great capability in distinguishing individual tumor histology with AUC values (95%CI) of 0.983 (0.985-0.989), 0.961 (0.957-0.964), 0.993 (0.992-0.994), 0.953 (0.947-0.958), 0.974 (0.970-0.978) and 0.980 (0.977-0.983) for normal WM, DC tumor, LDC tumor, infiltrating edge, necrosis and hemorrhage, respectively. Our results suggest that DBSI-DNN, or DHI, accurately characterized and classified multiple tumor histologic features in pediatric high-grade brain tumors. If further validated in patients, the novel DHI might emerge as a favorable alternative to the current neuroimaging techniques to better guide biopsy and resection as well as monitor therapeutic response in patients with high-grade brain tumors.

neuroscience↗