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1.
Circulation ; 149(18): 1405-1415, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38109351

ABSTRACT

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.


Subject(s)
Athletes , Cardiomyopathy, Dilated , Stroke Volume , Humans , Male , Cardiomyopathy, Dilated/genetics , Cardiomyopathy, Dilated/physiopathology , Cardiomyopathy, Dilated/diagnostic imaging , Female , Adult , Young Adult , Physical Endurance/genetics , Adolescent , Genetic Predisposition to Disease , Ventricular Remodeling , Ventricular Function, Left
2.
Ophthalmology ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38307466

ABSTRACT

PURPOSE: A recent genome-wide association study of age-related macular degeneration (AMD) identified new AMD-associated risk variants. These variants now can be incorporated into an updated polygenic risk score (PRS). This study aimed to assess the performance of an updated PRS, PRS2023, in an independent cohort of older individuals with retinal imaging data and to compare performance with an older PRS, PRS2016. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 4175 participants of European ancestry, 70 years of age or older, with genotype and retinal imaging data. METHODS: We used logistic regression models and area under the receiver operating characteristic curve (AUC) to assess the performance of PRS2023 compared with PRS2016. AMD status and severity were graded using color fundus photography. MAIN OUTCOME MEASURES: Association of PRS2023 and PRS2016 with AMD risk at baseline. RESULTS: At enrollment among 4175 participants, 2605 participants (62.4%) had no AMD and 853 participants (20.4%), 671 participants (16.1%), and 46 participants (1.1%) had early, intermediate, and late-stage AMD, respectively. More than 27% of the participants with a high PRS2023 (top quartile) had intermediate or late-stage AMD, compared with < 15% for those in the middle 2 quartiles and less than 13% for those in the lowest quartile. Both PRS2023 and PRS2016 were associated significantly with AMD after adjustment for age, sex, smoking status, and lipid levels, with increasing odds ratios (ORs) for worsening AMD grades. PRS2023 outperformed PRS2016 (P = 0.03 for all AMD and P = 0.03 for late AMD, DeLong test comparing AUC). PRS2023 was associated with late-stage AMD with an adjusted OR of 5.05 (95% confidence interval [CI], 3.41-7.47) per standard deviation. The AUC of a model containing conventional or nongenetic risk factors and PRS2023 was 91% (95% CI, 87%-95%) for predicting late-stage AMD, which improved 12% over the model without the PRS (AUC, 79%; P < 0.001 for difference). CONCLUSIONS: A new PRS, PRS2023, for AMD outperforms a previous PRS and predicts increasing risk for late-stage AMD (with stronger association for more severe imaging-confirmed AMD grades). Our findings have clinical implications for the improved prediction and risk stratification of AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

3.
Cytokine ; 174: 156471, 2024 02.
Article in English | MEDLINE | ID: mdl-38103301

ABSTRACT

The mammary gland is an adipose tissue containing not only adipocytes but also epithelial, endothelial, and immune cells. Epithelial cells and macrophages, as the integral components of the immune system, are on the front line of defense against infection. Our preliminary work proved that caffeic acid (CA) can effectively inhibit the inflammatory cascade of bovine mammary epithelial cells (BMEC) induced by lipopolysaccharide (LPS) and maintain cellular integrity and viability. Here, we investigated the therapeutic effect of CA on LPS-induced mice mastitis and explored its regulatory mechanism on macrophage inflammatory response induced by LPS in vitro. Firstly, the mice mastitis model was established by intramammary injection with 10 µg LPS, after which different CA doses (5, 10, 15 mg/kg) were administered. Then, the pathological section, myeloperoxidase (MPO) activity, proinflammatory factors and chemokines releasement, and redox state of mammary tissues were assessed, confirming CA's effectiveness on mice mastitis. In vitro, we validated the therapeutic relevance of CA in relieving LPS-induced RAW264.7 inflammatory and oxidative stress responses. Moreover, we further provided evidence that CA significantly reduced LPS-induced reactive oxygen species (ROS) generation via NADPH oxidase (NOX), which improved the imbalance relationship between nuclear factor kappa-B (NF-κB) and NF-E2 p45-related factor 2 (Nrf2) and led to a marked weakening of M1 polarization. The NOX-ROS signal inhibited by CA weakened the oxidative burst and neutrophil chemotaxis of macrophages, thus alleviating the immune cascade in mammary gland tissue and reducing the LPS-induced inflammatory damage. Collectively, CA would be a potential candidate or antibacterial synergist for curbing mastitis.


Subject(s)
Lipopolysaccharides , Mastitis , Humans , Female , Animals , Cattle , Mice , Lipopolysaccharides/adverse effects , Reactive Oxygen Species , NADPH Oxidases , Mastitis/chemically induced , Mastitis/drug therapy , NF-kappa B , Disease Models, Animal , Macrophages , Epithelial Cells
4.
Environ Sci Technol ; 58(22): 9669-9678, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38771965

ABSTRACT

In subsurface environments, Fe(II)-bearing clay minerals can serve as crucial electron sources for O2 activation, leading to the sequential production of O2•-, H2O2, and •OH. However, the observed •OH yields are notably low, and the underlying mechanism remains unclear. In this study, we investigated the production of oxidants from oxygenation of reduced Fe-rich nontronite NAu-2 and Fe-poor montmorillonite SWy-3. Our results indicated that the •OH yields are dependent on mineral Fe(II) species, with edge-surface Fe(II) exhibiting significantly lower •OH yields compared to those of interior Fe(II). Evidence from in situ Raman and Mössbauer spectra and chemical probe experiments substantiated the formation of structural Fe(IV). Modeling results elucidate that the pathways of Fe(IV) and •OH formation respectively consume 85.9-97.0 and 14.1-3.0% of electrons for H2O2 decomposition during oxygenation, with the Fe(II)edge/Fe(II)total ratio varying from 10 to 90%. Consequently, these findings provide novel insights into the low •OH yields of different Fe(II)-bearing clay minerals. Since Fe(IV) can selectively degrade contaminants (e.g., phenol), the generation of mineral Fe(IV) and •OH should be taken into consideration carefully when assessing the natural attenuation of contaminants in redox-fluctuating environments.


Subject(s)
Hydroxyl Radical , Minerals , Hydroxyl Radical/chemistry , Minerals/chemistry , Iron/chemistry , Clay/chemistry , Oxygen/chemistry , Hydrogen Peroxide/chemistry , Oxidation-Reduction , Aluminum Silicates/chemistry , Bentonite/chemistry
5.
Int J Cancer ; 153(3): 489-498, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-36919377

ABSTRACT

Methylation marks of exposure to health risk factors may be useful markers of cancer risk as they might better capture current and past exposures than questionnaires, and reflect different individual responses to exposure. We used data from seven case-control studies nested within the Melbourne Collaborative Cohort Study of blood DNA methylation and risk of colorectal, gastric, kidney, lung, prostate and urothelial cancer, and B-cell lymphoma (N cases = 3123). Methylation scores (MS) for smoking, body mass index (BMI), and alcohol consumption were calculated based on published data as weighted averages of methylation values. Rate ratios (RR) and 95% confidence intervals for association with cancer risk were estimated using conditional logistic regression and expressed per SD increase of the MS, with and without adjustment for health-related confounders. The contribution of MS to discriminate cases from controls was evaluated using the area under the curve (AUC). After confounder adjustment, we observed: large associations (RR = 1.5-1.7) with lung cancer risk for smoking MS; moderate associations (RR = 1.2-1.3) with urothelial cancer risk for smoking MS and with mature B-cell neoplasm risk for BMI and alcohol MS; moderate to small associations (RR = 1.1-1.2) for BMI and alcohol MS with several cancer types and cancer overall. Generally small AUC increases were observed after inclusion of several MS in the same model (colorectal, gastric, kidney, urothelial cancers: +3%; lung cancer: +7%; B-cell neoplasms: +8%). Methylation scores for smoking, BMI and alcohol consumption show independent associations with cancer risk, and may provide some improvements in risk prediction.


Subject(s)
Colorectal Neoplasms , Lung Neoplasms , Male , Humans , Body Mass Index , Cohort Studies , Smoking/adverse effects , Smoking/genetics , Risk Factors , Alcohol Drinking/adverse effects , DNA Methylation , Lung Neoplasms/etiology , Lung Neoplasms/genetics , Colorectal Neoplasms/genetics
6.
Environ Sci Technol ; 57(21): 8015-8025, 2023 05 30.
Article in English | MEDLINE | ID: mdl-37204932

ABSTRACT

Electron transfer (ET) is the essence of most biogeochemical processes related to element cycling and contaminant attenuation, whereas ET between different minerals and the controlling mechanism remain elusive. Here, we used surface-associated Fe(II) as a proxy to explore ET between reduced nontronite NAu-2 (rNAu-2) and Fe (hydr)oxides in their coexisting systems. Results showed that ET could occur from rNAu-2 to ferrihydrite but not to goethite, and the ET amount was determined by the number of reactive sites and the reduction potential difference between rNAu-2 and ferrihydrite. ET proceeded mainly through the mineral-mineral interface, with a negligible contribution of dissolved Fe2+/Fe3+. Control experiments by adding K+ and increasing salinity together with characterizations by X-ray diffraction, scanning electron microscopy/energy-dispersive spectrometry, and atomic force microscopy suggested that ferrihydrite nanoparticles inserted the interlayer space in rNAu-2 where structural Fe(II) in rNAu-2 transferred electrons mainly through the basal plane to ferrihydrite. This study implicates the occurrence of ET between different redox-active minerals through the mineral-mineral interface. As minerals at different reduction potentials often coexist in soils/sediments, the mineral-mineral ET may play an important role in subsurface biogeochemical processes.


Subject(s)
Iron , Oxides , Clay , Iron/chemistry , Electrons , Minerals/chemistry , Ferrous Compounds
7.
Alzheimers Dement ; 19(12): 5333-5342, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37177856

ABSTRACT

INTRODUCTION: Recent genome-wide association studies identified new dementia-associated variants. We assessed the performance of updated polygenic risk scores (PRSs) using these variants in an independent cohort. METHODS: We used Cox models and area under the curve (AUC) to validate new PRSs (PRS-83SNP, PRS-SBayesR, and PRS-CS) compared with an older PRS-23SNP in 12,031 initially-healthy participants ≥70 years of age. Dementia was rigorously adjudicated according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. RESULTS: PRS-83SNP, PRS-SBayesR, and PRS-CS were associated with incident dementia, with fully adjusted (including apolipoprotein E [APOE] ε4) hazard ratios per standard deviation (SD) of 1.35 (1.23-1.47), 1.37 (1.25-1.50), and 1.42 (1.30-1.56), respectively. The AUC of a model containing conventional/non-genetic factors and APOE was 74.7%. This was improved to 75.7% (p = 0.007), 76% (p = 0.004), and 76.1% (p = 0.003) with addition of PRS-83SNP, PRS-SBayesR, and PRS-CS, respectively. The PRS-23SNP did not improve AUC (74.7%, p = 0.95). CONCLUSION: New PRSs for dementia significantly improve risk-prediction performance, but still account for less risk than APOE genotype overall.


Subject(s)
Dementia , Genetic Risk Score , Humans , Prospective Studies , Genome-Wide Association Study , Apolipoproteins E/genetics , Dementia/genetics , Risk Factors
8.
Environ Sci Technol ; 56(18): 13408-13418, 2022 09 20.
Article in English | MEDLINE | ID: mdl-36063534

ABSTRACT

Hydrogen peroxide (H2O2) and hydroxyl radical (•OH) production during oxygenation of reduced iron (Fe(II)) and natural organic matter (NOM) in the subsurface has been increasingly discovered, whereas the effect of the C/Fe molar ratio in Fe(II) and NOM coexisting systems remains poorly understood. In this study, aqueous Fe(II) and reduced humic acid (HAred) mixture at different C/Fe molar ratios (0-20) were oxygenated. Results show that both H2O2 and •OH accumulation increased almost linearly with the increase in the C/Fe ratio, with a more prominent increase in •OH accumulation at high C/Fe molar ratios. At low C/Fe molar ratios (C/Fe ≤ 1.6), electrons mainly transferred from dissolved inorganic Fe(II), surface-adsorbed Fe(II), and a low proportion of HA-complexed Fe(II) to O2; with the increase in the C/Fe ratio to a high level (C/Fe ≥ 5), the main electron source turned to HA-complexed Fe(II) and free HAred. The changes in the electron source and electron transfer pathway with the increase in the C/Fe ratio increased the yield of •OH relative to H2O2. This study highlights the important role of the C/Fe ratio in controlling H2O2 and •OH production and therefore in accurately evaluating the associated environmental impacts.


Subject(s)
Humic Substances , Hydrogen Peroxide , Ferrous Compounds , Hydroxyl Radical , Iron , Oxidation-Reduction
9.
Environ Sci Technol ; 56(16): 11878-11887, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35938447

ABSTRACT

Dark formation of hydroxyl radicals (•OH) from soil/sediment oxygenation has been increasingly reported, and solid Fe(II) is considered as the main electron donor for O2 activation. However, the role of solid organic matter (SOM) in •OH production is not clear, although it represents an important electron pool in the subsurface. In this study, •OH production from oxygenation of reduced solid humic acid (HAred) was investigated at pH 7.0. •OH production is linearly correlated with the electrons released from HAred suspension. Solid HAred transferred electrons rapidly to O2 via the surface-reduced moieties (hydroquinone groups), which was fueled by the slow electron transfer from the reduced moieties inside solid HA. Cycling of dissolved HA between oxidized and reduced states could mediate the electron transfer from solid HAred to O2 for •OH production enhancement. Modeling results predicted that reduced SOM played an important or even dominant role in •OH production for the soils and sediments possessing high molar ratios of SOC/Fe(II) (e.g., >39). The significant contribution of SOM was further validated by the modeling results for oxygenation of 88 soils/sediments in the literature. Therefore, reduced SOM should be considered carefully to comprehensively understand •OH production in SOM-rich subsurface environments.


Subject(s)
Humic Substances , Hydroxyl Radical , Ferrous Compounds , Oxidation-Reduction , Soil
10.
Anal Chem ; 93(19): 7172-7179, 2021 05 18.
Article in English | MEDLINE | ID: mdl-33961391

ABSTRACT

Vanadium isotope compositions (δ(51V)) in marine carbonates are a potential proxy to trace global redox states of ancient oceans. Although high-precision δ(51V) analyses are available for many geological materials, carbonate-hosted δ(51V) data have not been reported yet due to extremely high matrix elements and low V contents (generally below 10 µg g-1). In this study, we developed an Fe coprecipitation method combined with an Fe column to preconcentrate V from the major matrix elements and subsequent four-step chromatographic procedures to further purify V in carbonates. The δ(51V) values were measured using a sample-standard bracketing method by MC-ICP-MS. The robustness of this method was assessed by analyzing element-doped and matrix-spiked synthetic carbonate solutions containing an in-house δ(51V) standard, USTC-V. The mean δ(51V) value of the synthetic carbonate solutions (0.06 ± 0.08‰; 2SD, n = 33) is in good agreement with the recommended value of the USTC-V relative to the Oxford AA solution (0.07 ± 0.08‰; 2SD, n = 347). In addition, the consistency in the δ(51V) value of the igneous carbonatite standard, COQ-1, which was processed in parallel with the whole purification (-0.48 ± 0.04‰; 2SD, n = 3) and a four-step chromatographic procedure (-0.43 ± 0.08‰; 2SD, n = 3), further validates the robustness of our method. For the first time, we obtained δ(51V) values of four carbonate reference materials: JDo-1, -0.56 ± 0.09‰ (2SD, n = 27); JLs-1, -0.61 ± 0.14‰ (2SD, n = 33); GBW07217a, -0.79 ± 0.09‰ (2SD, n = 6); GBW07214a, -0.51 ± 0.13‰ (2SD, n = 48). The long-term external precision of carbonate-hosted δ(51V) analyses is better than ±0.14‰ (2SD). Our method can be applied to measure carbonate-hosted δ(51V) to trace the evolution in global marine redox states throughout the Earth's history.

11.
Environ Sci Technol ; 55(19): 13366-13375, 2021 10 05.
Article in English | MEDLINE | ID: mdl-34551244

ABSTRACT

Hydroxyl radical (•OH) production by electron transfer from Fe(II)-bearing clay minerals to oxygen has been increasingly reported. However, the influence of ubiquitous coexisting humic acid (HA) on this process is poorly understood. Here, we investigated the effect of different HA on •OH production during the oxygenation of reduced nontronite NAu-2 (rNAu-2), montmorillonite, and sediment. Results showed that HA could enhance •OH production, and the enhancement was related to the content of reactive Fe(II) in rNAu-2 and the electron-accepting capacity of HA. Coexisting HA leads to a new electron-transfer pathway from Fe(II) in rNAu-2 to HA (instead of the HA-Fe complex) and then to O2, changing the first step of O2 reduction from one- to two-electron transfer process with H2O2 as the main intermediate. Reduced HA decomposes H2O2 to •OH at a higher yield (13.8%) than rNAu-2 (8.8%). Modeling results reveal that the HA-mediated electron-transfer pathway contributes to 12.6-70.2% of H2O2 generation and 13.2-62.1% of •OH formation from H2O2 decomposition, with larger contributions at higher HA concentrations (5-100 mg C/L). Our findings implicate that HA-mediated electron transfer can expand the area of •OH production from the mineral surface to the aqueous phase and increase the yield of •OH production.


Subject(s)
Humic Substances , Hydroxyl Radical , Clay , Ferric Compounds , Ferrous Compounds , Humic Substances/analysis , Hydrogen Peroxide , Minerals , Oxidation-Reduction
12.
Int J Mol Sci ; 22(5)2021 Mar 03.
Article in English | MEDLINE | ID: mdl-33802562

ABSTRACT

VTRNA2-1 is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DNA methylation in this region. We first sequenced the VTRNA2-1 gene region in multiple-case breast cancer families in which VTRNA2-1 methylation was identified as heritable and associated with breast cancer risk. Methylation quantitative trait loci (mQTL) were investigated using a prospective cohort study (4500 participants with genotyping and methylation data). The cis-mQTL analysis (334 variants ± 50 kb of the most heritable CpG site) identified 43 variants associated with VTRNA2-1 methylation (p < 1.5 × 10-4); however, these explained little of the methylation variation (R2 < 0.5% for each of these variants). No genetic variants elsewhere in the genome were found to strongly influence VTRNA2-1 methylation. SNP-based heritability estimates were consistent with the mQTL findings (h2 = 0, 95%CI: -0.14 to 0.14). We found no evidence that age, sex, country of birth, smoking, body mass index, alcohol consumption or diet influenced blood DNA methylation at VTRNA2-1. Genetic factors and adult lifestyle play a minimal role in explaining methylation variability at the heritable VTRNA2-1 cluster.


Subject(s)
DNA Methylation/genetics , MicroRNAs/genetics , Polymorphism, Single Nucleotide/genetics , Aged , Breast Neoplasms/genetics , Case-Control Studies , CpG Islands/genetics , Female , Genome-Wide Association Study/methods , Humans , Male , Middle Aged , Prospective Studies , Quantitative Trait Loci/genetics
13.
Biophys J ; 118(1): 70-84, 2020 01 07.
Article in English | MEDLINE | ID: mdl-31818466

ABSTRACT

STIM1 (a Ca2+ sensor in the endoplasmic reticulum (ER) membrane) and Orai1 (a pore-forming subunit of the Ca2+-release-activated calcium channel in the plasma membrane) diffuse in the ER membrane and plasma membrane, respectively. Upon depletion of Ca2+ stores in the ER, STIM1 translocates to the ER-plasma membrane junction and binds Orai1 to trigger store-operated Ca2+ entry. However, the motion of STIM1 and Orai1 during this process and its roles to Ca2+ entry is poorly understood. Here, we report real-time tracking of single STIM1 and Orai1 particles in the ER membrane and plasma membrane in living cells before and after Ca2+ store depletion. We found that the motion of single STIM1 and Orai1 particles exhibits anomalous diffusion both before and after store depletion, and their mobility-measured by the radius of gyration of the trajectories, mean-square displacement, and generalized diffusion coefficient-decreases drastically after store depletion. We also found that the measured displacement distribution is non-Gaussian, and the non-Gaussian parameter drastically increases after store depletion. Detailed analyses and simulations revealed that single STIM1 and Orai1 particles are confined in the compartmentalized membrane both before and after store depletion, and the changes in the motion after store depletion are explained by increased confinement and polydispersity of STIM1-Orai1 complexes formed at the ER-plasma membrane junctions. Further simulations showed that this increase in the confinement and polydispersity after store depletion localizes a rapid increase of Ca2+ influx, which can facilitate the rapid activation of local Ca2+ signaling pathways and the efficient replenishing of Ca2+ store in the ER in store-operated Ca2+ entry.


Subject(s)
Calcium/metabolism , ORAI1 Protein/metabolism , Stromal Interaction Molecule 1/metabolism , Biological Transport , Cell Membrane/metabolism , HEK293 Cells , Humans , Normal Distribution
15.
J Hum Genet ; 62(5): 577-580, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28148926

ABSTRACT

Major depressive disorder (MDD) is a common psychiatric illness with significant medical and socioeconomic impact. Genetic factors are likely to play important roles in the development of this condition. DNA sequencing technology has the ability to identify all private genetic mutations and provides new channels for studying the biology of MDD. In this proof-of-concept study we proposed a novel concept, single-nucleotide variant proportion (SNVP), to investigate MDD based on whole-genome sequencing (WGS) data. Our SNVP-based approach can be used to test newly found candidate genes as a complement to genome-wide genotyping analysis. Furthermore, we performed cluster analysis for MDD patients and ethnically matched healthy controls, and found that clusters based on SNVP may predict MDD diagnosis. Our results suggest that SNVP may be used as a potential biomarker associated with major depression. Our methodology could be a valuable predictive/diagnostic tool as one can test whether a new subject falls within or close to an existing MDD cluster. Advances in this study design have the potential to personalized treatments and could include the ability to diagnose patients based on their full or part DNA sequencing data.


Subject(s)
Depressive Disorder, Major/genetics , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing/methods , Polymorphism, Single Nucleotide/genetics , Humans
16.
J Theor Biol ; 406: 61-72, 2016 10 07.
Article in English | MEDLINE | ID: mdl-27375217

ABSTRACT

The alignment-free n-gram based method with the out-of-place measures as the distance has been successfully applied to automatic text or natural languages categorization in real time. However, it is not clear about its performance and the selection of n for comparing genome sequences. Here we propose a symmetric version of the out-of-place measure and a new approach for finding the optimal range of n to construct a phylogenetic tree with the symmetric out-of-place measures. Our method is then applied to real genome sequence datasets. The resulting phylogenetic trees are matching with the standard biological classification. It shows that our proposed method is a very powerful tool for phylogenetic analysis in terms of both classification accuracy and computation efficiency.


Subject(s)
Computational Biology/methods , DNA, Mitochondrial/genetics , Sequence Alignment/methods , Animals , Archaea/genetics , Base Sequence , Cluster Analysis , Humans , Likelihood Functions , Phylogeny , Primates/genetics , RNA, Ribosomal, 16S/genetics , Vertebrates/genetics
17.
J Theor Biol ; 372: 135-45, 2015 May 07.
Article in English | MEDLINE | ID: mdl-25747773

ABSTRACT

A novel clustering method is proposed to classify genes and genomes. For a given DNA sequence, a binary indicator sequence of each nucleotide is constructed, and Discrete Fourier Transform is applied on these four sequences to attain respective power spectra. Mathematical moments are built from these spectra, and multidimensional vectors of real numbers are constructed from these moments. Cluster analysis is then performed in order to determine the evolutionary relationship between DNA sequences. The novelty of this method is that sequences with different lengths can be compared easily via the use of power spectra and moments. Experimental results on various datasets show that the proposed method provides an efficient tool to classify genes and genomes. It not only gives comparable results but also is remarkably faster than other multiple sequence alignment and alignment-free methods.


Subject(s)
DNA/genetics , Sequence Analysis, DNA/methods , Algorithms , Animals , Bacteria/genetics , Cluster Analysis , Computational Biology , Coronavirus/genetics , DNA, Mitochondrial/genetics , Evolution, Molecular , Fourier Analysis , Genome , Genome, Bacterial , Humans , Image Processing, Computer-Assisted , Influenza A virus/genetics , Models, Genetic , Phylogeny , Rhinovirus/genetics , Sequence Alignment/methods
18.
Mol Phylogenet Evol ; 81: 29-36, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25172357

ABSTRACT

We have recently developed a computational approach in a vector space for genome-based virus classification. This approach, called the "Natural Vector (NV) representation", which is an alignment-free method, allows us to classify single-segmented viruses with high speed and accuracy. For multiple-segmented viruses, typically phylogenetic trees of each segment are reconstructed for discovering viral phylogeny. Consensus tree methods may be used to combine the phylogenetic trees based on different segments. However, consensus tree methods were not developed for instances where the viruses have different numbers of segments or where their segments do not match well. We propose a novel approach for comparing multiple-segmented viruses globally, even in cases where viruses contain different numbers of segments. Using our method, each virus is represented by a set of vectors in R(12). The Hausdorff distance is then used to compare different sets of vectors. Phylogenetic trees can be reconstructed based on this distance. The proposed method is used for predicting classification labels of viruses with n-segments (n ⩾ 1). The correctness rates of our predictions based on cross-validation are as high as 96.5%, 95.4%, 99.7%, and 95.6% for Baltimore class, family, subfamily, and genus, respectively, which are comparable to the rates for single-segmented viruses only. Our method is not affected by the number or order of segments. We also demonstrate that the natural graphical representation based on the Hausdorff distance is more reasonable than the consensus tree for a recent public health threat, the influenza A (H7N9) viruses.


Subject(s)
Genome, Viral , Influenza A Virus, H7N9 Subtype/classification , Phylogeny , Sequence Analysis, DNA/methods , Genomics/methods , Influenza A Virus, H7N9 Subtype/genetics , Viruses/classification , Viruses/genetics
19.
J Theor Biol ; 348: 12-20, 2014 May 07.
Article in English | MEDLINE | ID: mdl-24486229

ABSTRACT

In this paper, we develop a novel method to study the viral genome phylogeny. We apply Lempel-Ziv complexity to define the distance between two nucleic acid sequences. Then, based on this distance we use the Hausdorff distance (HD) and a modified Hausdorff distance (MHD) to make the phylogenetic analysis for multi-segmented viral genomes. The results show the MHD can provide more accurate phylogenetic relationship. Our method can have global comparison of all multi-segmented genomes simultaneously, that is, we treat the multi-segmented viral genome as an entirety to make the comparative analysis. Our method is not affected by the number or order of segments, and each segment can make contribution for the phylogeny of whole genomes. We have analyzed several groups of real multi-segmented genomes from different viral families. The results show that our method will provide a new powerful tool for studying the classification of viral genomes and their phylogenetic relationships.


Subject(s)
Genome, Viral , Sequence Analysis, DNA/methods , Animals , Base Sequence , DNA, Viral/genetics , Databases, Nucleic Acid , HIV-1/classification , HIV-1/genetics , Phylogeny , Simian Immunodeficiency Virus/classification , Simian Immunodeficiency Virus/genetics
20.
ScientificWorldJournal ; 2014: 208765, 2014.
Article in English | MEDLINE | ID: mdl-25165735

ABSTRACT

As an advanced process detection technology, electrical impedance tomography (EIT) has widely been paid attention to and studied in the industrial fields. But the EIT techniques are greatly limited to the low spatial resolutions. This problem may result from the incorrect preprocessing of measuring data and lack of general criterion to evaluate different preprocessing processes. In this paper, an EIT data preprocessing method is proposed by all rooting measured data and evaluated by two constructed indexes based on all rooted EIT measured data. By finding the optimums of the two indexes, the proposed method can be applied to improve the EIT imaging spatial resolutions. In terms of a theoretical model, the optimal rooting times of the two indexes range in [0.23, 0.33] and in [0.22, 0.35], respectively. Moreover, these factors that affect the correctness of the proposed method are generally analyzed. The measuring data preprocessing is necessary and helpful for any imaging process. Thus, the proposed method can be generally and widely used in any imaging process. Experimental results validate the two proposed indexes.


Subject(s)
Algorithms , Electric Impedance , Electronic Data Processing/methods , Models, Theoretical , Tomography/methods , Signal-To-Noise Ratio , Time Factors
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