RESUMO
DNA-templated nanofabrication presents an innovative approach to creating self-assembled nanoscale metal-semiconductor-based Schottky contacts, which can advance nanoelectronics. Herein, we report the successful fabrication of metal-semiconductor Schottky contacts using a DNA origami scaffold. The scaffold, consisting of DNA strands organized into a specific linear architecture, facilitates the competitive arrangement of Au and CdS nanorods, forming heterojunctions, and addresses previous limitations in low electrical conductance making DNA-templated electronics with semiconductor nanomaterials. Electroless gold plating extends the Au nanorods and makes the necessary electrical contacts. Tungsten electrical connection lines are further created by electron beam-induced deposition. Electrical characterization reveals nonlinear Schottky barrier behavior, with electrical conductance ranging from 0.5 × 10-4 to 1.7 × 10-4 S. The conductance of these DNA-templated junctions is several million times higher than with our prior Schottky contacts. Our research establishes an innovative self-assembly approach with applicable metal and semiconductor materials for making highly conductive nanoscale Schottky contacts, paving the way for the future development of DNA-based nanoscale electronics.
Assuntos
Compostos de Cádmio , DNA , Ouro , Semicondutores , Sulfetos , Ouro/química , Compostos de Cádmio/química , Sulfetos/química , DNA/química , Nanotecnologia/métodos , Condutividade ElétricaRESUMO
The discovery of new drugs has important implications for human health. Traditional methods for drug discovery rely on experiments to optimize the structure of lead molecules, which are time-consuming and high-cost. Recently, artificial intelligence has exhibited promising and efficient performance for drug-like molecule generation. In particular, deep generative models achieve great success in de novo generation of drug-like molecules with desired properties, showing massive potential for novel drug discovery. In this study, we review the recent progress of molecule generation using deep generative models, mainly focusing on molecule representations, public databases, data processing tools, and advanced artificial intelligence based molecule generation frameworks. In particular, we present a comprehensive comparison of state-of-the-art deep generative models for molecule generation and a summary of commonly used molecular design strategies. We identify research gaps and challenges of molecule generation such as the need for better databases, missing 3D information in molecular representation, and the lack of high-precision evaluation metrics. We suggest future directions for molecular generation and drug discovery.
Assuntos
Inteligência Artificial , Benchmarking , Humanos , Bases de Dados Factuais , Descoberta de Drogas , Desenho de FármacosRESUMO
Anaerobic digestion of phenolic wastewater by anaerobic membrane bioreactor (AnMBR) has revealed increasing attractiveness, but the application of AnMBRs for treating high-strength phenolic wastewater faces challenges related to elevated phenol stress and membrane fouling. In this study, the coupling of AnMBR and polyaluminum chloride (PAC) was developed for efficient treatment of high-strength phenolic wastewater. The system achieved robust removal efficiencies of phenol (99%) and quinoline (98%) at a gradual increase of phenol concentration from 1000 to 5000 mg/L and a constant quinoline concentration of 100 mg/L. The dosing of PAC could effectively control the membrane fouling rate with the transmembrane pressure (TMP) increasing rate as low as 0.17 kPa/d. The robust performances were mainly attributed to the favorable retention of functional microbes through membrane interception, while pulse cross flow buffered against phenol stress and facilitated cake layer removal. Meanwhile, the enriched core functional microbes, such as Syntrophorhabdus, Syntrophus, Mesotoga and Methanolinea, played a crucial role in further reduction of phenol stress. Notably, the significant presence of biomacromolecule degrader, such as Levilinea, contributed to membrane fouling mitigation through extracellular polymer degradation. Moreover, the enlargement of particle size distribution (PSD) by PAC was expected to mitigate membrane fouling. This study provided a promising avenue for sustainable treatment of high-strength phenolic wastewater.
Assuntos
Reatores Biológicos , Membranas Artificiais , Eliminação de Resíduos Líquidos , Águas Residuárias , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Hidróxido de Alumínio/química , Fenóis/análise , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Spinal meningiomas coexisting with schwannomas in patients without neurofibromatosis are extremely rare lesions. There were only 15 cases reported to date, which were concurrent intradural tumors of different pathological types. CASE PRESENTATION: Herein, we present a rare case of a 15-year-old child with concurrent spinal dorsal meningioma and ventral giant invasive schwannoma at C7-T3 and T10-S5 spinal levels. Preoperative magnetic resonance imaging and computed tomography indicated the schwannoma across the thoracic and lumbosacral transitional vertebra, with extensive bony erosion of the sacrum. The results of surgical resection were mostly satisfactory. CONCLUSIONS: The present case is the youngest patient diagnosed with concurrent intradural tumors at different spinal levels. The pathogenetic mechanism remains unclear. The clinical presentations are always atypical. Surgical resection of the tumors is the first choice. We use the non-fusion surgery to preserve the function of the lumbar spine.
Assuntos
Neoplasias Meníngeas , Meningioma , Neurilemoma , Neurofibromatoses , Neoplasias da Coluna Vertebral , Adolescente , Humanos , Neoplasias Meníngeas/complicações , Meningioma/cirurgia , Neurilemoma/patologia , Neurofibromatoses/complicações , Neoplasias da Coluna Vertebral/cirurgiaRESUMO
To address the problem that complex bearing faults are coupled to each other, and the difficulty of diagnosis increases, an improved envelope spectrum-maximum second-order cyclostationary blind deconvolution (IES-CYCBD) method is proposed to realize the separation of vibration signal fault features. The improved envelope spectrum (IES) is obtained by integrating the part of the frequency axis containing resonance bands in the cyclic spectral coherence function. The resonant bands corresponding to different fault types are accurately located, and the IES with more prominent target characteristic frequency components are separated. Then, a simulation is carried out to prove the ability of this method, which can accurately separate and diagnose fault types under high noise and compound fault conditions. Finally, a compound bearing fault experiment with inner and outer ring faults is designed, and the inner and outer ring fault characteristics are successfully separated by the proposed IES-CYCBD method. Therefore, simulation and experiments demonstrate the strong capability of the proposed method for complex fault separation and diagnosis.
RESUMO
PURPOSE: The removal of small foreign bodies embedded within the deep soft tissues of the maxillofacial region is a complex and challenging task for maxillofacial surgeons. The purpose of this study was to explore the efficacy of the combination of intraoperative CT and surgical navigation for the removal of small foreign objects in the maxillofacial region. METHODS: A serial case study was conducted involving all consecutive patients who underwent surgical removal of small foreign bodies in the maxillofacial region. The combination of intraoperative CT and a surgical navigation system was used at a single medical institution from January 2018 to December 2022. Comprehensive data, including patient demographics, characteristics of the foreign bodies, previous surgical interventions, duration of the surgical procedure, and removal success rate were collected for this study. Relevant data were recorded into Microsoft Excel sheet and analyzed using SPSS version 22.0. RESULTS: Nine patients (6 males and 3 females) were included in this study, with an average age of 37 years. Each patient had previously undergone an unsuccessful removal attempt utilizing conventional surgical methods based on preoperative CT imaging or C-arm guidance at a local healthcare facility. Four patients also experienced unsuccessful attempts with preoperative CT image-based navigation systems. However, by employing the combined approach of intraoperative CT and surgical navigation, the foreign bodies were successfully removed in all 9 patients. The mean duration of the surgical procedure was 59 min, and the average size of the foreign bodies was approximately 26 mm³. Postoperative follow-up exceeding 6 months revealed no complications. CONCLUSION: The combined use of a surgical navigation system and intraoperative CT represents a potent and effective strategy for the precise localization and subsequent removal of small foreign bodies from the soft tissue structures of the maxillofacial region. This integrative approach appears to increase the success rate of surgical interventions in such cases.
RESUMO
Rapid and accurate antimicrobial prescriptions are critical for bloodstream infection (BSI) patients, as they can guide drug use and decrease mortality significantly. The traditional antimicrobial susceptibility testing (AST) for BSI is time-consuming and tedious, taking 2-3 days. Avoiding lengthy monoclonal cultures and shortening the drug sensitivity incubation time are keys to accelerating the AST. Here, we introduced a bacteria separation integrated AST (BSI-AST) chip, which could extract bacteria directly from positive blood cultures (PBCs) within 10 min and quickly give susceptibility information within 3 h. The integrated chip includes a bacteria separation chamber, multiple AST chambers, and connection channels. The separator gel was first preloaded into the bacteria separation chamber, enabling the swift separation of bacteria cells from PBCs through on-chip centrifugation. Then, the bacteria suspension was distributed in the AST chambers with preloaded antibiotics through a quick vacuum-assisted aliquoting strategy. Through centrifuge-assisted on-chip enrichment, detectable growth of the phenotype under different antibiotics could be easily observed in the taper tips of AST chambers within a few hours. As a proof of concept, direct AST from artificial PBCs with Escherichia coli against 18 antibiotics was performed on the BSI-AST chip, and the whole process from bacteria extraction to AST result output was less than 3.5 h. Moreover, the integrated chip was successfully applied to the diagnosis of clinical PBCs, showing 93.3% categorical agreement with clinical standard methods. The reliable and fast pathogen characterization of the integrated chip suggested its great potential application in clinical diagnosis.
Assuntos
Hemocultura , Sepse , Humanos , Microfluídica , Antibacterianos/farmacologia , Centrifugação , Escherichia coliRESUMO
Lung adenocarcinoma (LUAD) is usually found at the metastatic stage. Circular RNA dihydrouridine synthase 2-like (DUS2L) (circDUS2L) has been discovered to be upregulated in LUAD. Nevertheless, the function of circDUS2L in LUAD has not been verified. Levels of circDUS2L, microRNA-590-5p (miR-590-5p), and phosphoglycerate mutase 1 (PGAM1) mRNA were analyzed using quantitative real-time polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, metastasis, and invasion were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), colony formation, 5-ethynyl-2'-deoxyuridine (Edu), flow cytometry, and transwell assays. Protein levels were detected by western blotting. Cell glycolysis was analyzed by measuring cell glucose consumption, lactate production, and extracellular acidification rate (ECAR). The regulatory mechanism of circDUS2L in LUAD cells was analyzed by bioinformatics analysis, dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. Xenograft assay was conducted to confirm the function of circDUS2L in vivo. CircDUS2L was highly expressed in LUAD tissues and cells. CircDUS2L silencing constrained xenograft tumor growth in vivo. CircDUS2L knockdown induced apoptosis, repressed viability, colony formation, proliferation, metastasis, invasion, and glycolysis of LUAD cells in vitro by releasing miR-590-5p via functioning as a miR-590-5p sponge. MiR-590-5p was lowly expressed in LUAD tissues and cells, and miR-590-5p mimic curbed malignant behaviors and glycolysis of LUAD cells by targeting PGAM1. PGAM1 was overexpressed in LUAD tissues and cells, and circDUS2L sponged miR-590-5p to regulate PGAM1 expression. CircDUS2L elevated PGAM1 expression through functioning as a miR-590-5p sponge, thus driving malignant behaviors and glycolysis of LUAD cells.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , MicroRNAs , Humanos , Fosfoglicerato Mutase/genética , Adenocarcinoma de Pulmão/genética , RNA Circular/genética , Proliferação de Células , Neoplasias Pulmonares/genética , MicroRNAs/genética , Linhagem Celular TumoralRESUMO
Mitochondrial dynamics, including mitochondrial fission and fusion, are critical for maintaining mitochondrial functions. Evidence shows that TANK-binding kinase 1 (TBK1) regulates mitochondrial fusion and fission and then mitophagy. Since a previous study demonstrates a strong correlation between mitophagy and osteoarthritis (OA), we herein investigated the potential role of TBK1 in OA process and mitochondrial functions. We demonstrated a strong correlation between TBK1 and OA, evidenced by significantly downregulated expression of TBK1 in cartilage tissue samples of OA patients and in the chondrocytes of aged mice, as well as TNF-α-stimulated phosphorylation of TBK1 in primary mouse chondrocytes. TBK1 overexpression significantly attenuated TNF-α-induced apoptosis and abnormal mitochondrial function in primary mouse chondrocytes. Furthermore, TBK1 overexpression induced remodeling of mitochondrial morphology by directly phosphorylating dynamin-related protein 1 (DRP1) at Ser637, abolishing the fission of DRP1 and preventing its fragmentation function. Moreover, TBK1 recruitment and DRP1 phosphorylation at Ser637 was necessary for engulfing damaged mitochondria by autophagosomal membranes during mitophagy. Moreover, we demonstrated that APMK/ULK1 signaling contributed to TBK1 activation. In OA mouse models established by surgical destabilization of the medial meniscus, intraarticular injection of lentivirus-TBK1 significantly ameliorated cartilage degradation via regulation of autophagy and alleviation of cell apoptosis. In conclusion, our results suggest that the TBK1/DRP1 pathway is involved in OA and pharmacological targeting of the TBK1-DRP1 cascade provides prospective therapeutic benefits for the treatment of OA.
Assuntos
Dinâmica Mitocondrial , Fator de Necrose Tumoral alfa , Camundongos , Animais , Fosforilação , Fator de Necrose Tumoral alfa/metabolismo , Autofagia/fisiologia , Dinaminas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
KEY MESSAGE: An autopolyploid-suitable polyBSA-seq strategy was developed for screening candidate genetic markers linked to leaf blight resistance in sugarcane. Due to the complex genome architecture, the quantitative trait loci mappings and linkage marker selections for agronomic traits of autopolyploid crops were mainly limited to the time-consuming and cost intensive construction of genetic maps. To map resistance-linked markers for sugarcane leaf blight (SLB) caused by Stagonospora tainanensis, the autopolyploid-suitable bulk-segregant analysis based on the sequencing (polyBSA-seq) strategy was successfully applied for the first time. Resistant- and susceptible-bulks (R- and S-bulks) constructed from the extreme-phenotypic sugarcane F1 lines of YT93-159 × ROC22 were deep sequenced with 195.0 × for bulks and 74.4 × for parents. Informative single-dose variants (ISDVs) present as one copy in one parent and null in the other parent were detected based on the genome sequence of LA Purple, an autooctoploid Saccharum officinarum, to screen candidate linkage markers (CLMs). The proportion of the number of short reads harboring ISDVs in the total short reads covering a given genomic position was defined as ISDV index and the ISDVs with indices met the threshold set in this study (0.04-0.14) were selected as CLMs. In total, three resistance- and one susceptibility-related CLMs for SLB resistance were identified by the polyBSA-seq. Among them, two markers on chromosome 10 were less than 300 Kb apart. Furthermore, the RNA-seq was used to calculate the expression level of genes within 1.0 Mb from the aforementioned four CLMs, which demonstrated that twelve genes were differentially expressed between resistant and susceptible clones, including a receptor-like kinase and an ethylene-responsive transcription factor. This is the first reported polyBSA-seq in autopolyploid sugarcane, which specifically tailored for the fast selection of the CLMs and causal genes associated with important agronomic traits.
Assuntos
Saccharum , Mapeamento Cromossômico , Ligação Genética , Marcadores Genéticos , Fenótipo , Saccharum/genéticaRESUMO
A three-component [3 + 2 + 1] annulation strategy for the synthesis of biologically and pharmaceutically active 2,3-diarylpyridine derivatives by using a series of allylic alcohols, ketones, and ammonium acetate as substrates has been developed. The method proceeds efficiently under metal-free conditions, and the desired heterocycles could be obtained in a site-specific selectivity manner with good functional group tolerance.
RESUMO
Solid-phase extraction (SPE) is a general preconcentration method for sample preparation that can be performed on a variety of specimens. The miniaturization of SPE within a 3D printed microfluidic device further allows for fast and simple extraction of analytes while also enabling integration of SPE with other sample preparation and separation methods. Here, we present the development and application of a reversed-phase lauryl methacrylate-based monolith, formed in 3D printed microfluidic devices, which can selectively retain peptides and proteins. The effectiveness of these SPE monoliths and 3D printed microfluidic devices was tested using a panel of nine preterm birth biomarkers of varying hydrophobicities and ranging in mass from 2 to 470 kDa. The biomarkers were selectively retained, fluorescently labeled, and eluted separately from the excess fluorescent label in 3D printed microfluidic systems. These are the first results demonstrating microfluidic analysis processes on a complete panel of preterm birth biomarkers, an important step toward developing a miniaturized, fully integrated analysis system.
Assuntos
Fluorescência , Dispositivos Lab-On-A-Chip , Nascimento Prematuro/diagnóstico , Impressão Tridimensional , Extração em Fase Sólida , Biomarcadores/análise , Corantes Fluorescentes/química , HumanosRESUMO
MOTIVATION: The volume and complexity of biological data increases rapidly. Many clinical professionals and biomedical researchers without a bioinformatics background are generating big '-omics' data, but do not always have the tools to manage, process or publicly share these data. RESULTS: Here we present MOLGENIS Research, an open-source web-application to collect, manage, analyze, visualize and share large and complex biomedical datasets, without the need for advanced bioinformatics skills. AVAILABILITY AND IMPLEMENTATION: MOLGENIS Research is freely available (open source software). It can be installed from source code (see http://github.com/molgenis), downloaded as a precompiled WAR file (for your own server), setup inside a Docker container (see http://molgenis.github.io), or requested as a Software-as-a-Service subscription. For a public demo instance and complete installation instructions see http://molgenis.org/research.
Assuntos
Biologia Computacional , Software , Algoritmos , Genoma , GenômicaRESUMO
(1) Background: Upland cotton (Gossypium hirsutum L.) is the most important natural fiber worldwide, and it is extensively planted and plentifully used in the textile industry. Major cotton planting regions are frequently affected by abiotic stress, especially drought stress. Drought resistance is a complex, quantitative trait. A genome-wide association study (GWAS) constitutes an efficient method for dissecting the genetic architecture of complex traits. In this study, the drought resistance of a population of 316 upland cotton accessions was studied via GWAS. (2) Methods: GWAS methodology was employed to identify relationships between molecular markers or candidate genes and phenotypes of interest. (3) Results: A total of 8, 3, and 6 SNPs were associated with the euphylla wilting score (EWS), cotyledon wilting score (CWS), and leaf temperature (LT), respectively, based on a general linear model and a factored spectrally transformed linear mixed model. For these traits, 7 QTLs were found, of which 2 each were located on chromosomes A05, A11, and D03, and of which 1 was located on chromosome A01. Importantly, in the candidate regions WRKY70, GhCIPK6, SnRK2.6, and NET1A, which are involved in the response to abscisic acid (ABA), the mitogen-activated protein kinase (MAPK) signaling pathway and the calcium transduction pathway were identified in upland cotton at the seedling stage under drought stress according to annotation information and linkage disequilibrium (LD) block analysis. Moreover, RNA sequencing analysis showed that WRKY70, GhCIPK6, SnRK2.6, and NET1A were induced by drought stress, and the expression of these genes was significantly different between normal and drought stress conditions. (4) Conclusions: The present study should provide some genomic resources for drought resistance in upland cotton. Moreover, the germplasm of the different phenotypes, the detected SNPs and, the potential candidate genes will be helpful for molecular marker-assisted breeding studies about increased drought resistance in upland cotton.
Assuntos
Gossypium/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Plântula/genética , Adaptação Fisiológica , Secas , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Gossypium/fisiologia , Desequilíbrio de Ligação , Plântula/fisiologia , Estresse FisiológicoRESUMO
MOTIVATION: Biobanks are indispensable for large-scale genetic/epidemiological studies, yet it remains difficult for researchers to determine which biobanks contain data matching their research questions. RESULTS: To overcome this, we developed a new matching algorithm that identifies pairs of related data elements between biobanks and research variables with high precision and recall. It integrates lexical comparison, Unified Medical Language System ontology tagging and semantic query expansion. The result is BiobankUniverse, a fast matchmaking service for biobanks and researchers. Biobankers upload their data elements and researchers their desired study variables, BiobankUniverse automatically shortlists matching attributes between them. Users can quickly explore matching potential and search for biobanks/data elements matching their research. They can also curate matches and define personalized data-universes. AVAILABILITY AND IMPLEMENTATION: BiobankUniverse is available at http://biobankuniverse.com or can be downloaded as part of the open source MOLGENIS suite at http://github.com/molgenis/molgenis. CONTACT: m.a.swertz@rug.nl. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Biologia Computacional/métodos , Bases de Dados Factuais , Software , AlgoritmosRESUMO
Distributed long-range Brillouin optical time domain analysis (BOTDA) is an extremely time-consuming sensing scheme, which requires frequency mapping of the Brillouin spectrum and a large number of average times. Here, we propose a fast long-range BOTDA based on the optical chirp chain (OCC) probe wave and Brillouin loss scheme. The OCC-modulated probe wave is enabled by cascading fast-frequency-changing microwave chirp segments head-to-tail, which covers a large frequency range around the anti-Stokes frequency relative to the pump wave. The combination of the OCC technique and Brillouin loss scheme provides several advantages, i.e., fast measurement, a high Brillouin threshold, no additional amplification scheme, and freedom from the nonlocal effect. In the experiment, 6 m spatial resolution, 3.2 s measurement time, and 3 MHz measurement precision were achieved over a 150 km single-mode fiber.
RESUMO
OBJECTIVE: To investigate the association of change in waist circumference (WC) and incidence of dyslipidaemia in a cohort study of a rural Chinese population. METHODS: Change in WC (ΔWC) was defined as the value at follow-up minus the corresponding value at baseline. Risk of dyslipidaemia associated with ΔWC was assessed by odds ratios and 95% confidence intervals in a logistic regression model, and the odds ratios were transformed to relative risks (RRs). RESULTS: Among 7691 participants without dyslipidaemia at baseline, 3213 (41.78%) showed dyslipidaemia at 6 year follow-up. Risk of dyslipidaemia was decreased for participants with the first quartile of ΔWC and normal baseline WC (adjusted RR [aRR] = 0.79 [95% confidence interval: 0.64-0.98]) and was increased with the fourth quartile of ΔWC and male gender, age 18 to 30 years, age 31 to 50 years, or normal baseline WC (aRR = 1.55 [1.19-2.03], 2.40 [1.16-4.95], 1.32 [1.06-1.64], and 1.66 [1.35-2.04], respectively). The risk of dyslipidaemia increased with change in WC from normal at baseline to abnormal at follow-up for both genders (aRR = 1.88 [1.39-2.55] for men and 1.60 [1.30-1.97] for women) and decreased with abnormal baseline WC changed to normal WC for women (aRR = 0.61 [0.45-0.83]). CONCLUSIONS: Dynamic change in waist circumference was closely related to the incidence of dyslipidaemia in a rural Chinese population. Waist circumference reduction could decrease dyslipidaemia risk, whereas WC increase may increase the risk. Interventions to control or reduce WC to within the normal range are important for early prevention of dyslipidaemia.
Assuntos
Povo Asiático/estatística & dados numéricos , Índice de Massa Corporal , Dislipidemias/epidemiologia , Circunferência da Cintura , Adulto , China/epidemiologia , Estudos de Coortes , Dislipidemias/etiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , População RuralRESUMO
This paper presents a new method that complements current techniques available in the high-frequency blood imaging field. A comprehensive scattering model was established to determine the feasibility and frequency range of the blood flow imaging of superficial organs and tissues using high-frequency ultrasound. The transmitting and receiving modes and an algorithm were designed to obtain blood flow information based on differentiation between tissues and blood flow. The system was created and tested first with a model that simulates blood flow and was then used on human tissue. A fine-scale image of a blood vessel could be obtained with this system. Moreover, this method can obtain weak blood flow signal using single pulse rather than the traditional pulse-code method and maintains a high resolution that can be matched to high-frequency structural imaging. This study provides a reliable method for further applications related to diagnoses of superficial organs.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Mãos/irrigação sanguínea , Processamento de Sinais Assistido por Computador , Ultrassonografia/métodos , Mãos/diagnóstico por imagem , HumanosRESUMO
MOTIVATION: While the size and number of biobanks, patient registries and other data collections are increasing, biomedical researchers still often need to pool data for statistical power, a task that requires time-intensive retrospective integration. RESULTS: To address this challenge, we developed MOLGENIS/connect, a semi-automatic system to find, match and pool data from different sources. The system shortlists relevant source attributes from thousands of candidates using ontology-based query expansion to overcome variations in terminology. Then it generates algorithms that transform source attributes to a common target DataSchema. These include unit conversion, categorical value matching and complex conversion patterns (e.g. calculation of BMI). In comparison to human-experts, MOLGENIS/connect was able to auto-generate 27% of the algorithms perfectly, with an additional 46% needing only minor editing, representing a reduction in the human effort and expertise needed to pool data. AVAILABILITY AND IMPLEMENTATION: Source code, binaries and documentation are available as open-source under LGPLv3 from http://github.com/molgenis/molgenis and www.molgenis.org/connect CONTACT: : m.a.swertz@rug.nl SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Assuntos
Bancos de Espécimes Biológicos , Biologia Computacional/métodos , Fenótipo , Software , Algoritmos , Ontologias Biológicas , HumanosRESUMO
BACKGROUND: Several prediction tools have been developed to identify people with type 2 diabetes mellitus (T2DM) and to quantify the probability of developing T2DM. However, most of the risk models were constructed based on cross-sectional studies and tea-drinking was not included. METHODS: A total of 15 768 participants without known T2DM were followed up from 2007-2008 to 2013-2014; 12 654 were randomly assigned to the derivation dataset and 3114 to the validation dataset. We constructed a risk-score model for T2DM by using a Cox proportional-hazards model. Risk scores were calculated by multiplying ß by 10 in the derivation cohort and were verified in the validation dataset. The model's accuracy was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: Predictors for T2DM risk in the derivation dataset were drinking tea frequently, body mass index ≥28.0 kg/m2 , waist to height ratio ≥ 0.5, triglycerides level 1.70 to 2.25 and ≥2.26 mmol/L, and fasting plasma glucose 5.6 to 6.0 and ≥6.1 mmol/L. The corresponding scores were -2, 7, 7, 4, 6, 11, and 25, respectively. The sensitivity, specificity, and AUC (95% confidence interval) for this full model were 69.63%, 75.56%, and 0.791 (0.783-0.799), respectively. The ability of the non-invasive models to predict T2DM was not superior to that of the full model. With the validation dataset, the predictive performance was better for our full model than the Framingham risk-score model (AUC 0.731 vs 0.525, P < .001). CONCLUSIONS: Our risk-score model has fair efficacy for predicting 6-year risk of T2DM in a rural adult Chinese population.