Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 73
Filter
1.
J Cogn Neurosci ; 36(5): 854-871, 2024 05 01.
Article in English | MEDLINE | ID: mdl-38307125

ABSTRACT

Analogical reasoning is central to thought and learning. However, previous neuroscience studies have focused mainly on neural substrates for visuospatial and semantic analogies. There has not yet been research on the neural correlates of analogical reasoning on syntactic patterns generated by the syntactic rules, a key feature of human language faculty. The present investigation took an initial step to address this paucity. Twenty-four participants, whose brain activity was monitored by fMRI, engaged in first-order and second-order relational judgments of syntactic patterns as well as simple and complex working memory tasks. After scanning, participants rated the difficulty of each step during analogical reasoning; these ratings were related to signal intensities in activated regions of interest using Spearman correlation analyses. After prior research, differences in activation levels during second-order and first-order relational judgments were taken as evidence of analogical reasoning. These analyses showed that analogical reasoning on syntactic patterns recruited brain regions consistent with those supporting visuospatial and semantic analogies, including the anterior and posterior parts of the left middle frontal gyrus, anatomically corresponding to the left rostrolateral pFC and the left dorsolateral pFC. The correlation results further revealed that the posterior middle frontal gyrus might be involved in analogical access and mapping with syntactic patterns. Our study is the first to investigate the process of analogical reasoning on syntactic patterns at the neurobiological level and provide evidence of the specific functional roles of related regions during subprocesses of analogical reasoning.


Subject(s)
Brain , Problem Solving , Humans , Problem Solving/physiology , Brain/diagnostic imaging , Frontal Lobe/physiology , Brain Mapping , Magnetic Resonance Imaging
2.
Appl Spectrosc ; 78(4): 423-437, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38373441

ABSTRACT

The present work is aimed at studying how spatially periodic modulations of the refractive index of the medium, i.e., laser-induced gratings (LIGs), generated in a gas mixture containing methane (CH4) by nanosecond pulses of resonant mid-infrared laser radiation, can be used to measure various gas parameters. It is investigated to what extent the temporal profiles of the LIG signals, recorded as the power of the diffracted by LIGs continuous wave probe radiation, are specific to the composition, pressure, and temperature of a selected buffer gas. This specificity is illustrated by the LIG signal profiles recorded in the experiments in different gas mixtures under various conditions. Experimental data show that large LIG signals can be obtained even in mixtures with CH4 concentrations as low as ∼100 parts per million due to the strong absorption of the excitation light and subsequent rapid, highly exothermic, and partner-dependent collisional energy exchange of the laser-excited molecules with the environment. These two factors ensure high LIG generation efficiency by a small number of CH4 molecules and high sensitivity of signal strength and profile to variations of gas parameters.

3.
Sci Bull (Beijing) ; 69(8): 1071-1080, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38302332

ABSTRACT

The commercialization of lithium-sulfur (Li-S) batteries has been hindered by the shuttle effect and sluggish redox kinetics of lithium polysulfides (LiPSs). Herein, we reported a viologen-based ionic conjugated mesoporous polymer (TpV-Cl), which acts as the cathode host for modifying Li-S batteries. The viologen component serves as a reversible electron conveyer, leading to a comprehensive enhancement in the adsorption of polysulfides and improved conversion rate of polysulfides during the electrochemical process. As a result, the S@TpV-PS cathode exhibits outstanding cycling performance, achieving 300 cycles at 2.0 C (1 C = 1675 mA g-1) with low decay rate of 0.032% per cycle. Even at a high sulfur loading of 4.0 mg cm-2, S@TpV-PS shows excellent cycling stability with a Coulombic efficiency of up to 98%. These results highlight the significant potential of S@TpV-PS in developing high-performance Li-S batteries.

4.
Clin Immunol ; 255: 109739, 2023 10.
Article in English | MEDLINE | ID: mdl-37586671

ABSTRACT

Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.


Subject(s)
Sjogren's Syndrome , Humans , Sjogren's Syndrome/diagnostic imaging , Sjogren's Syndrome/genetics , Transcriptome , Salivary Glands/diagnostic imaging , Ultrasonography/methods , Biomarkers
5.
IEEE Trans Neural Netw Learn Syst ; 34(8): 4981-4989, 2023 Aug.
Article in English | MEDLINE | ID: mdl-34855601

ABSTRACT

In many practical applications, it is difficult or impossible to obtain the exact solution of the mathematical model due to the limitations of solving methods and the complexity of the neural network itself. A natural problem is given as follows: does the exact solution of quaternion-valued neural networks (QVNNs) exist when successively improved approximate solutions can be obtained? Fortunately, the Hyers-Ulam stability happens to be one of the important means to deal with this problem. In this article, the issue of Hyers-Ulam stability of QVNNs with time-varying delays is addressed. First, inspired by the Hyers-Ulam stability of general functional equations, the concept of the Hyers-Ulam stability of QVNNs is proposed along with the QVNNs model. Then, by utilizing the successive approximation method, both delay-dependent and delay-independent Hyers-Ulam stability criteria are obtained to ensure the Hyers-Ulam stability of the QVNNs considered. Finally, a simulation example is given to verify the effectiveness of the derived results.

6.
Appl Opt ; 61(25): 7361-7365, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36256035

ABSTRACT

Visualization of the reaction zone of flames using CH radicals as markers is restricted by the low concentration of CH in fuel-lean conditions. To address this, methyl radicals (CH3) are employed as a substitution of CH in premixed methane/air flames. A pump-probe method was adopted with the pump laser photolyzing CH3 and the probe laser detecting the photolyzed CH (X2Π) fragments. Laser excitation scans were performed to ensure that the fluorescence detected was from CH only. Visualization of the reaction zone of flames was accomplished by a CH3 photofragmentation laser-induced fluorescence technique in fuel-lean conditions (the equivalence ratio of 0.4), where CH planar laser-induced fluorescence did not work in both laminar and turbulent jet flames. The proposed pump-probe method of CH3 can be used to visualize the reaction zone of hydrocarbon combustion under both fuel-lean and fuel-rich conditions with a superior signal-to-noise ratio.

7.
Front Psychol ; 13: 835147, 2022.
Article in English | MEDLINE | ID: mdl-35295390

ABSTRACT

In school education, teaching-learning interaction is deemed as a core process in the classroom. The fundamental neural basis underlying teaching-learning interaction is proposed to be essential for tuning learning outcomes. However, the neural basis of this process as well as the relationship between the neural dynamics and the learning outcomes are largely unclear. With non-invasive technologies such as fNIRS (functional near-infrared spectroscopy), hyperscanning techniques have been developed since the last decade and been applied to the field of educational neuroscience for simultaneous multi-brain scanning. Hyperscanning studies suggest that the interpersonal neural synchronization (INS) during teaching-learning interaction might be an ideal neural biomarker for predicting learning outcomes. To systematically evaluate such a relationship, this meta-analysis ran on a random-effects model on 16 studies with 23 independent samples (effect sizes). Further moderator analyses were also performed to examine the potential influences of the style, mode, content, and the assessment method of learning outcomes. The random-effects modeling results confirmed a robust positive correlation between INS and learning outcomes. Subsequent analyses revealed that such relationship was mainly affected by both interaction style and mode. Therefore, the present meta-analysis provided a confirmatory neurocognitive foundation for teaching-learning interaction, as well as its relation to the learning outcomes, consolidated future learning and teaching studies in various disciplines including second language education with a firm methodological reference.

8.
Adv Mater ; 34(11): e2109496, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35020258

ABSTRACT

Circularly polarized luminescence (CPL) switches have attracted widespread attention due to their potential applications in advanced information technologies. However, the design and fabrication of solid-state multiple-responsive CPL switches remain challenging. Here, through self-assembly of chiral metal-organic frameworks (MOFs) and perovskite nanocrystals (NCs), a pair of crystalline enantiomeric (P)-(+)/(M)-(-)-EuMOF⊃MAPbX3 (MA = CH3 NH3 + , X = Cl- , Br- , I- ) adducts is prepared, where the achiral MAPbBr3 perovskite NCs embedded into chiral MOFs inherit the chirality of host MOFs by host-guest EuBr and PbO coordination bonds, which is demonstrated by synchrotron-radiation-based X-ray absorption spectroscopy. The chiral adducts show enhanced photoluminescence quantum yield (PLQY), good thermal stability of CPL in air, and photoswitchable CPL properties upon altering different UV irradiation. Based on two chiral emission centers and their different characteristics, reversible CPL switches are realized upon a diversity of external stimuli, for example, chemicals (water /CH3 NH3 Br solution) or temperatures (room temperature/high temperature). Benefiting from the extraordinary stimuli-responsive and highly reversible switchable CPL, multiple information encryptions and decryptions integrated with CPL, together with a chiroptical logic gate are successfully designed. This work opens a new avenue to generally fabricate solid-state CPL composite materials and develops new applications based on switchable CPL.

9.
Appl Spectrosc ; 76(2): 207-215, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34981992

ABSTRACT

Hydrogen chloride (HCl) monitoring during combustion/gasification of biomass fuels and municipal solid waste, such as polyvinyl chloride (PVC) and food residues, is demanded to avoid the adverse effect of HCl to furnace operation and to improve the quality of the gas products. Infrared tunable diode laser absorption spectroscopy (IR-TDLAS) is a feasible nonintrusive in-situ method for HCl measurements in harsh environments. In the present work, the measurement was performed using the R(3) line of the ν2 vibrational band of HCl at 5739.25 cm-1 (1742.4 nm). Water vapor is ubiquitous in combustion/gasification environments, and its spectral interference is one of the most common challenges for IR-TDLAS. Spectral analysis based on the current well-known databases was found to be insufficient to achieve an accurate measurement. The lack of accurate temperature-dependent water spectra can introduce thousands parts per million (ppm) HCl overestimation. For the first time, accurate spectroscopic data of temperature-dependent water spectra near 5739.3 cm-1 were obtained based on a systematic experimental investigation of the hot water lines in a well-controlled, hot flue gas with a temperature varying from 1100 to 1950 K. With the accurate knowledge of hot water interference, the HCl TDLAS system can achieve a detection limit of about 100 ppm⋅m at around 1500 K, and simultaneously the gas temperature can be derived. The technique was applied to measure the temporally resolved HCl release and local temperature over burning PVC particles in hot flue gas at 1790 K.

10.
Genomics Proteomics Bioinformatics ; 20(2): 260-273, 2022 04.
Article in English | MEDLINE | ID: mdl-34252627

ABSTRACT

Periodontitis is an inflammatory disease that is characterized by progressive destruction of the periodontium and causes tooth loss in adults. Periodontitis is known to be associated with dysbiosis of the oral microflora, which is often linked to various diseases. However, the complexity of plaque microbial communities of periodontitis, antibiotic resistance, and enhanced virulence make this disease difficult to treat. In this study, using metagenomic shotgun sequencing, we investigated the etiology, antibiotic resistance genes (ARGs), and virulence genes (VirGs) of periodontitis. We revealed a significant shift in the composition of oral microbiota as well as several functional pathways that were represented significantly more abundantly in periodontitis patients than in controls. In addition, we observed several positively selected ARGs and VirGs with the Ka/Ks ratio > 1 by analyzing our data and a previous periodontitis dataset, indicating that ARGs and VirGs in oral microbiota may be subjected to positive selection. Moreover, 5 of 12 positively selected ARGs and VirGs in periodontitis patients were found in the genomes of respiratory tract pathogens. Of note, 91.8% of the background VirGs with at least one non-synonymous single-nucleotide polymorphism for natural selection were also from respiratory tract pathogens. These observations suggest a potential association between periodontitis and respiratory infection at the gene level. Our study enriches the knowledge of pathogens and functional pathways as well as the positive selection of antibiotic resistance and pathogen virulence in periodontitis patients, and provides evidence at the gene level for an association between periodontitis and respiratory infection.


Subject(s)
Microbiota , Periodontitis , Humans , Adult , Metagenome , Metagenomics , Periodontitis/complications , Periodontitis/genetics , Dysbiosis , Anti-Bacterial Agents
11.
Opt Express ; 29(21): 34465-34476, 2021 Oct 11.
Article in English | MEDLINE | ID: mdl-34809236

ABSTRACT

In this work, the combustion behavior of seeded iron particles (d50 = 70 µm) in a laminar diffusion flame was studied in a modified Mckenna flat-flame burner. Two high speed cameras in stereo configuration allowed 3D position and 3D velocity measurements of burning iron particles as well as 3D evaluation of particle microexplosions. Microexplosive processes are important since it can affect both combustion stability and formation of product components. The observed microexplosions happened before particle extinction resulting in change of trajectories, velocities, radiation intensities and fragmentation into smaller particles. It was observed for the first time that fragments of these microexplosions tend to produce planar structures. A frequent release phenomenon was observed during the iron particle combustion using magnified thermal radiation imaging and high-speed shadowgraphy. This release phenomenon was indirectly confirmed with scanning electron microscopy of combust products, revealing multiple cracked particle shells and hollow structures. Black body radiation characteristics was observed indicating the release being in condensed phase and emission spectroscopy identified FeO as intermediate species during combustion. The observed release is believed to mainly consist of iron-oxide nanoparticles formed in the homogenous reaction between vapor iron and oxidizers.

12.
Appl Spectrosc ; 75(11): 1402-1409, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34477464

ABSTRACT

We report the observation of photoluminescence emission from airborne gold, silver, and copper nanoparticles. A continuous wave 532 nm laser was employed for excitation. Photoluminescence from gold nanoparticles carried in a nitrogen gas flow was both spectrally resolved and directly imaged in situ using an intensified charge-coupled device camera. The simultaneously detected Raman signal from the nitrogen molecules enables quantitative estimation of the photoluminescence quantum yield of the gold nanoparticles. Photoluminescence from metal nanoparticles carried in a gas flow provides a potential tool for operando imaging of plasmonic metal nanoparticles in aerosol reactions.

13.
Energy Fuels ; 35(9): 7179-7192, 2021 May 06.
Article in English | MEDLINE | ID: mdl-34054210

ABSTRACT

This paper presents a joint experimental and numerical study on premixed laminar ammonia/methane/air flames, aiming to characterize the flame structures and NO formation and determine the laminar flame speed under different pressure, equivalence ratio, and ammonia fraction in the fuel. The experiments were carried out in a lab-scale pressurized vessel with a Bunsen burner installed with a concentric co-flow of air. Measurements of NH and NO distributions in the flames were made using planar laser-induced fluorescence. A novel method was presented for determination of the laminar flame speed from Bunsen-burner flame measurements, which takes into account the non-uniform flow in the unburned mixture and local flame stretch. NH profiles were chosen as flame front markers. Direct numerical simulation of the flames and one-dimensional chemical kinetic modeling were performed to enhance the understanding of flame structures and evaluate three chemical kinetic mechanisms recently reported in the literature. The stoichiometric and fuel-rich flames exhibit a dual-flame structure, with an inner premixed flame and an outer diffusion flame. The two flames interact, which affects the NO emissions. The impact of the diffusion flame on the laminar flame speed of the inner premixed flame is however minor. At elevated pressures or higher ammonia/methane ratios, the emission of NO is suppressed as a result of the reduced radical mass fraction and promoted NO reduction reactions. It is found that the laminar flame speed measured in the present experiments can be captured by the investigated mechanisms, but quantitative predictions of the NO distribution require further model development.

14.
Sci Rep ; 11(1): 9829, 2021 May 10.
Article in English | MEDLINE | ID: mdl-33972614

ABSTRACT

Laser-induced grating spectroscopy (LIGS) is for the first time explored in a configuration based on the crossing of two focused femtosecond (fs) laser pulses (800-nm wavelength) and a focused continuous-wave (cw) laser beam (532-nm wavelength). A thermal grating was formed by multi-photon absorption of the fs-laser pulses by [Formula: see text] with a pulse energy around 700 [Formula: see text]J ([Formula: see text] 45 TW/[Formula: see text]). The feasibility of this LIGS configuration was investigated for thermometry in heated nitrogen gas flows. The temperature was varied from room temperature up to 750 K, producing strong single-shot LIGS signals. A model based on the solution of the linearized hydrodynamic equations was used to extract temperature information from single-shot experimental data, and the results show excellent agreement with the thermocouple measurements. Furthermore, the fluorescence produced by the fs-laser pulses was investigated. This study indicates an 8-photon absorption pathway for [Formula: see text] in order to reach the [Formula: see text] state from the ground state, and 8 + 5 photon excitation to reach the [Formula: see text] state of the [Formula: see text] ion. At pulse energies higher than 1 mJ, the LIGS signal was disturbed due to the generation of plasma. Additionally, measurements in argon gas and air were performed, where the LIGS signal for argon shows lower intensity compared to air and [Formula: see text].

15.
Appl Spectrosc ; 75(9): 1168-1177, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33464157

ABSTRACT

Ammonia (NH3) is regarded as an important nitrogen oxides (NOx) precursor and also as an effective reductant for NOx removal in energy utilization through combustion, and it has recently become an attractive non-carbon alternative fuel. To have a better understanding of thermochemical properties of NH3, accurate in situ detection of NH3 in high temperature environments is desirable. Ultraviolet (UV) absorption spectroscopy is a feasible technique. To achieve quantitative measurements, spectrally resolved UV absorption cross-sections of NH3 in hot gas environments at different temperatures from 295 K to 590 K were experimentally measured for the first time. Based on the experimental results, vibrational constants of NH3 were determined and used for the calculation of the absorption cross-section of NH3 at high temperatures above 590 K using the PGOPHER software. The investigated UV spectra covered the range of wavelengths from 190 nm to 230 nm, where spectral structures of the A∼ 1A″2X∼ 1A'1 transition of NH3 in the umbrella bending mode, v2, were recognized. The absorption cross-section was found to decrease at higher temperatures. For example, the absorption cross-section peak of the (6, 0) vibrational band of NH3 decreases from ∼2 × 10-17 to ∼0.5 × 10-17 cm2/molecule with the increase of temperature from 295 K to 1570 K. Using the obtained absorption cross-section, in situ nonintrusive quantification of NH3 in different hot gas environments was achieved with a detection limit varying from below 10 parts per million (ppm) to around 200 ppm as temperature increased from 295 K to 1570 K. The quantitative measurement was applied to an experimental investigation of NH3 combustion process. The concentrations of NH3 and nitric oxide (NO) in the post flame zone of NH3-methane (CH4)-air premixed flames at different equivalence ratios were measured.

16.
Article in English | MEDLINE | ID: mdl-32929885

ABSTRACT

Neurodevelopmental disorders, including autism spectrum disorder (ASD), intellectual disability (ID), developmental disorders (DD) and epileptic encephalopathy (EE), have a strong clinical comorbidity, which indicates a common genetic etiology across various disorders. However, the underlying genetic mechanisms of comorbidity and specificity remain unknown across neurodevelopmental disorders. Based on de novo mutations, we compared systematically the functional characteristics between shared and unique genes under these disorders, as well as the spatiotemporal trajectory of development in brain and common molecular pathways of all shared genes. We observed that shared genes present more constrained against functional rare genetic variation, and harbor more pathogenic rare variants than do unique genes in each disorder. Furthermore, 71 shared genes formed two clusters related to synaptic transmission, transcription regulation and chromatin regulator. Particularly, we also found that two core genes STXBP1 and SCN2A, that were shared by the four neurodevelopmental disorders showed prominent pleiotropy. Our findings shed light on the shared and specific patterns across neurodevelopmental disorders and will enable us to further comprehend the etiology and provide valuable information for the diagnosis of neurodevelopmental disorders.


Subject(s)
Autism Spectrum Disorder/genetics , Brain Diseases/genetics , Developmental Disabilities/genetics , Epilepsy/genetics , Intellectual Disability/genetics , Munc18 Proteins/genetics , NAV1.2 Voltage-Gated Sodium Channel/genetics , Autism Spectrum Disorder/pathology , Brain Diseases/pathology , Case-Control Studies , Developmental Disabilities/pathology , Epilepsy/pathology , Humans , Intellectual Disability/pathology , Neurodevelopmental Disorders/classification , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/pathology
17.
Appl Spectrosc ; 75(1): 107-114, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33021109

ABSTRACT

It has previously been demonstrated that the ratio of the degenerate four wave mixing signal from two hot water line groups near 3231 cm-1 can be used for seedless flame temperature measurements. This paper presents an investigation of the impact of saturation effects on the measured signal intensity from each line group, as well as an estimation of the accuracy of the method. The saturation effects observed here would result in a large systematic error if they are not taken into account when using the degenerate four-wave mixing intensity of these water line groups to calculate the flame temperature.

18.
Nat Genet ; 52(9): 939-949, 2020 09.
Article in English | MEDLINE | ID: mdl-32601472

ABSTRACT

N6-methyladenosine (m6A) plays important roles in regulating messenger RNA processing. Despite rapid progress in this field, little is known about the genetic determinants of m6A modification and their role in common diseases. In this study, we mapped the quantitative trait loci (QTLs) of m6A peaks in 60 Yoruba (YRI) lymphoblastoid cell lines. We found that m6A QTLs are largely independent of expression and splicing QTLs and are enriched with binding sites of RNA-binding proteins, RNA structure-changing variants and transcriptional features. Joint analysis of the QTLs of m6A and related molecular traits suggests that the downstream effects of m6A are heterogeneous and context dependent. We identified proteins that mediate m6A effects on translation. Through integration with data from genome-wide association studies, we show that m6A QTLs contribute to the heritability of various immune and blood-related traits at levels comparable to splicing QTLs and roughly half of expression QTLs. By leveraging m6A QTLs in a transcriptome-wide association study framework, we identified putative risk genes of these traits.


Subject(s)
Adenosine/analogs & derivatives , RNA, Messenger/genetics , Adenosine/genetics , Chromosome Mapping/methods , Genetic Testing/methods , Genetic Variation/genetics , Genome-Wide Association Study/methods , Humans , Phenotype , Quantitative Trait Loci/genetics , Quantitative Trait, Heritable , RNA Splicing/genetics , Transcriptome/genetics
19.
Sensors (Basel) ; 20(10)2020 May 14.
Article in English | MEDLINE | ID: mdl-32423122

ABSTRACT

Measurement of acoustic waves from laser-induced breakdown has been developed as gas thermometry in combustion atmospheres. In the measurement, two laser-induced breakdown spots are generated and the local gas temperature between these two spots is determined through the measurement of the sound speed between them. In the previous study, it was found that the local gas breakdown can introduce notable system uncertainty, about 5% to the measured temperature. To eliminate the interference, in present work, a new measurement procedure was proposed, where two individual laser pulses with optimized firing order and delay time were employed. With the new measurement procedure, the system uncertainty caused by local gas breakdown can be largely avoided and the temporal and spatial resolutions can reach up to 0.5 ms and 10 mm, respectively. The improved thermometry, dual-laser-induced breakdown thermometry (DLIBT), was applied to measure temperatures of hot flue gases provided by a multijet burner. The measured temperatures covering the range between 1000 K and 2000 K were compared with the ones accurately obtained through the two-line atomic fluorescence (TLAF) thermometry with a measurement uncertainty of ~3%, and a very good agreement was obtained.

20.
Genet Med ; 22(1): 170-180, 2020 01.
Article in English | MEDLINE | ID: mdl-31332282

ABSTRACT

PURPOSE: Elucidating the genetic architecture underlying autism spectrum disorder (ASD) will aid in the understanding of its genetic etiology and clinical diagnosis. METHODS: A comprehensive set of coding de novo variants (DNVs) from 4504 trios with ASD and 3012 control/sibling trios from several large-scale sequencing studies were collected and combined. Multiple in-depth analyses including DNVs burden, clinical phenotypes, and functional networks underlying the combined data set were used to evaluate the nonrandom occurrence of multiple extreme DNVs (loss-of-function and damaging missense variants) in the same patients. RESULTS: We observed a significant excess of multiple extreme DNVs among patients with ASD compared with controls. Meanwhile, patients with ASD carrying 2+ extreme DNVs had significantly lower IQs than patients carrying 0 or 1 DNV. Moreover, much closer functional connectivity than expected was observed among 2 or more genes with extreme DNVs from the same individuals. In particular, we identified 56 key genes as more confident ASD genes compared with other known ASD genes. In addition, we detected 23 new ASD candidate genes with recurrent DNVs, including VIP, ZWILCH, MSL2, LRRC4, and CAPRIN1. CONCLUSIONS: Our findings present compelling statistical evidence supporting an oligogenic model and provide new insights into the genetic architecture of ASD.


Subject(s)
Autism Spectrum Disorder/genetics , Multifactorial Inheritance , Mutation, Missense , Sequence Analysis, DNA/methods , Autism Spectrum Disorder/psychology , Case-Control Studies , Female , Gene Regulatory Networks , Genetic Predisposition to Disease , Humans , Intelligence Tests , Loss of Function Mutation , Male , Models, Genetic
SELECTION OF CITATIONS
SEARCH DETAIL
...