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Biomedical subjects

Pei Wang

Publications and source records attributed to Pei Wang.

At least 19 recordsLinked to original sources

Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets.

High-grade gliomas (HGGs) in children and adolescents and young adults (AYA) exhibit distinct biology across the neurodevelopmental spectrum. To dissect tumor-intrinsic molecular characteristics independent of developmental variation, we perform comprehensive proteogenomic analyses of tumors from 112 HGG patients aged 0-40 years. Our multi-omics analysis identifies two AYA subgroups-adolescents (aged 15-26 years) and young adults (aged 26-40 years)-with distinct molecular profiles and survival outcomes. Tumor-normal comparisons and survival modeling highlight roles of oxidative phosphorylation and neuronal system biology in glioma progression. Causal network analysis and cell line studies provide a rationale for personalized therapies targeting candidate kinases, such as CDK8. Survival modeling, clustering, and immune-landscape analyses identify proteins, post-translational modifications, and immune signatures linked to outcomes and reveal clinically relevant differences between male and female patients.

adolescent and young adult glioma↗

Natural language processing-based model to predict radiation pneumonitis in patients with locally advanced non-small cell lung cancer undergoing chemoradiotherapy: a retrospective cohort study.

BACKGROUND: Radiation pneumonitis (RP) remains a significant treatment-related toxicity in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) undergoing chemoradiotherapy (CRT). Most existing predictive models rely on static baseline demographic or dosimetry variables and lack real-time clinical applicability. We developed a novel predictive framework that integrates longitudinal symptom data extracted from clinical notes using natural language processing (NLP) with clinical and dosimetry features to improve early RP prediction. METHODS: We retrospectively identified 227 patients with locally advanced NSCLC treated with definitive CRT at a high-volume cancer center in the United States. We included all patients older than 18 years who were diagnosed between Jan 1, 2006, and Dec 31, 2022 with histologically or cytologically confirmed unresectable Stage 2 or 3 NSCLC and treated with conformal radiotherapy to a minimum dose of ≥45 Gy with or without chemotherapy. Of these, 31 RP events were identified through manual adjudication using radiologic criteria and chart review. NLP was used to extract the temporal relationship of 16 pre-specified symptoms with treatment from over 100,000 clinical notes spanning pre- and during-treatment intervals. We trained and validated machine learning models on combinations of baseline clinical data, radiation dosimetry, and NLP-derived symptom features. Model performance was evaluated using a nested cross-validation framework, with an outer cross-validation loop reserved for performance assessment and an inner cross-validation loop used for model training and integration, and summarized using area under the receiver operating characteristic curve (AUC) and partial AUC (pAUC) at high specificity thresholds. Clinical utility was evaluated using decision curve analysis (DCA). FINDINGS: The best-performing model incorporated longitudinal NLP features and achieved a median AUC of 0.759 (90% confidence interval 0.753-0.766), significantly outperforming baseline models using only dosimetry (AUC 0.613) or clinical variables (AUC 0.635). NLP-based features such as cough trajectory, shortness of breath, and wheezing were among the most important predictors. Inclusion of NLP-derived symptom data improved early identification of high-risk patients, particularly in the clinically relevant high-specificity range (pAUC 0.021 vs. 0.010 for dosimetry alone). DCA showed that the calibrated MLP model provided greater net benefit than default strategies of treating all or no patients across clinically relevant threshold possibilities. INTERPRETATION: In this early work, NLP-based extraction of longitudinal symptoms from routine clinical documentation meaningfully enhances RP prediction in patients undergoing CRT for NSCLC. This approach leverages existing electronic health record infrastructure to deliver real-time, scalable, and interpretable risk estimates, offering a pathway toward potential early intervention and personalized toxicity management. The model and DCA requires external and prospective validation before clinical deployment; as such, future work should focus on this validation and integration into clinical decision support systems. FUNDING: AstraZeneca.

Chemoradiotherapy↗

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12 weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32 mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n = 119) or the sevelamer carbonate group (n = 120). The mean change in serum phosphorus levels was -0.70 ± 0.50 mmol/L in the ferric citrate group and -0.61 ± 0.59 mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09 mmol/L; 95% CI, -0.24 to 0.05 mmol/L; non-inferiority margin, 0.32 mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p = 0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult↗

Bidirectional causal relationships between plasma proteins, neuroimaging metrics and risk of Alzheimer's disease.

BACKGROUND: Changes in neuroimaging metrics are among the first detectable pathophysiological alterations in Alzheimer's disease (AD). Proteins are closely linked to fluctuations in neuroimaging metrics. Therefore, the analysis of the proteomic signature associated with neuroimaging metrics holds significant promise for uncovering therapeutic targets that contribute to AD. METHODS: GWAS data concerning the Brain Imaging Data Structure (BIDs). The AD cohort comprised a total of 401,661 individuals diagnosed with AD, alongside 10,520 control participants. For a bidirectional MR analysis involving neuroimaging metrics, proteomics, and AD, the methods utilized included inverse variance weighted (IVW), MR Egger, weighted median, weighted mode, and the Wald ratio approaches. RESULTS: We identified 12 neuroimaging metrics that demonstrate significant relevance to AD (thickness of the left total hemisphere, volume of the right thalamus, and et al.). These metrics are structural magnetic resonance imaging (MRI) biomarkers that remain stable throughout the entire course of AD, from the preclinical stage through mild cognitive impairment (MCI) to dementia. Additionally, we found a substantial number of 1633 proteins that also show a noteworthy causal relationship with AD. Functional enrichment analysis indicated that these proteins were predominantly focused within various pathways linked to AD, encompassing those involved in the synaptic vesicle cycle, synaptic membranes, neurotransmitter release, and the activity of GABA receptors. In addition, our research indicates that the significant relationships observed between the identified proteins and AD are influenced by neuroimaging metrics. Notably, we found that these neuroimaging metrics play a crucial role in mediating a substantial 67% of the inverse relationship that exists between PTPRC and the phenotypic characteristics associated with AD. CONCLUSIONS: This study successfully establishes a connection between proteomic and neuroimaging metrics, as well as the AD that influence them. By creating this relationship, the research offers important information that aids in comprehending the intricate mechanisms involved in AD.

Alzheimer Disease↗

Stable chloroform emissions in southeastern China: insights from recent observations.

Chloroform (CHCl3) is a short-lived ozone-depleting substance not currently regulated under the Montreal Protocol. Due to the unique meteorological conditions in East Asia, CHCl3 emitted in this region has a greater potential to reach the stratosphere and contribute to ozone depletion. As an essential component of national CHCl3 emissions, southeastern China has attracted increasing attention. However, long-term observational data in this region remain relatively scarce, with no updates since 2020. In this study, we continuously measured atmospheric CHCl3 concentrations at a remote monitoring station in southeastern China from 1 June 2023 to 31 May 2025. Frequent concentration enhancements were observed during the monitoring period, with mixing ratios ranging from 9.3 to 134.1 ppt and an average value of 36.8 ± 19.7 ppt. Back-trajectory analysis indicated that air masses associated with elevated CHCl3 levels primarily originated from coastal industrial provinces in eastern China. Using the Potential Source Contribution Function and Concentration Weighted Trajectory methods, we identified the Yangtze River Delta (Jiangsu, Anhui, and Zhejiang Provinces) and Jiangxi Province as dominant source regions. Emissions of CHCl3 in southeastern China were estimated using the Tracer Ratio Method to be approximately 30.1 ± 5.3 Gg/yr from 2023-06-01 to 2025-05-31, indicating overall stability relative to earlier estimates and no apparent upward trend. These findings provide updated insights into the current status of CHCl3 emissions in southeastern China and highlight the need for continued monitoring and emission assessment of CHCl3 in East Asia, given its unregulated status and implications for ozone layer recovery.

Air Pollutants↗

Treatment preference for once-weekly versus once-daily DPP-4 inhibitors in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Although once-weekly and once-daily DPP-4 inhibitors have gained widespread market recognition, patient preference differences remain a key focus. This meta-analysis compares treatment preferences for once-weekly versus once-daily DPP-4 inhibitors in T2DM, offering evidence to guide clinical decisions and healthcare policies. METHODS: PubMed, OVID, EBSCO, Web of Science, CNKI, Wanfang, and clinical trial registries were searched up to June 30, 2025. After screening literature against predefined criteria, a systematic review was conducted to compare the effects of once-weekly and once-daily DPP-4 inhibitors on the treatment preferences of patients with T2DM. RESULTS: 8 RCTs with 1,575 participants were analyzed. No significant difference in medication adherence and DTSQ total score between the once-weekly and once-daily groups (p > 0.05). HbA1c percentage (MD = -0.21, 95% CI [-0.42, -0.01], p < 0.05) decreased significantly with once-weekly dosing, while GA and FPG showed no change (p > 0.05), this suggests greater improvement in HbA1c percentage levels following a switch to once-weekly DPP-4 inhibitors. Once-weekly DPP-4 inhibitors showed higher musculoskeletal/connective tissue disorder risk (RR = 2.63; 95% CI [1.18, 5.83]), but no significant differences in other adverse events (p > 0.05). No significant differences in treatment burden between both groups (p > 0.05). CONCLUSION: No statistically significant association between treatment preferences for once-weekly versus once-daily DPP-4 inhibitors among T2DM patients and medication adherence, treatment satisfaction, glycemic level changes, safety, or treatment burden for these two dosing regimens. Further research is needed to elucidate the influence of physician prescribing behavior on these preferences.

Humans↗

Learning directed acyclic graphs for ligands and receptors based on spatially resolved transcriptomic data of ovarian cancer.

To unravel the mechanism of immune activation and suppression within tumors, a critical step is to identify transcriptional signals governing cell-cell communication between tumor and immune/stromal cells in the tumor microenvironment. Central to this communication are interactions between secreted ligands and cell-surface receptors, creating a highly connected signaling network among cells. Recent advancements in in situ-omics profiling, particularly spatial transcriptomic (ST) technology, provide unique opportunities to directly characterize ligand-receptor signaling networks that power cell-cell communication. In this paper, we propose a novel statistical method, LRnetST, to characterize the ligand-receptor interaction networks between adjacent tumor and immune/stroma cells based on ST data. LRnetST utilizes a directed acyclic graph model with a novel approach to handle the zero-inflated distributions of ST data. It also leverages existing ligand-receptor regulation databases as prior information, and employs a bootstrap aggregation strategy to achieve robust network estimation. Application of LRnetST to ST data of high-grade serous ovarian tumor samples revealed both common and distinct ligand-receptor regulations across different tumors. Some of these interactions were validated through both a MERFISH dataset and a CosMx SMI dataset of independent ovarian tumor samples. These results cast light on biological processes relating to the communication between tumor and immune/stromal cells in ovarian tumors. An open-source R package of LRnetST is available on GitHub at https://github.com/jie108/LRnetST.

Humans↗

Effects of early enteral arginine supplementation on resuscitation of severe burn patients.

OBJECTIVES: To investigate the effects of dietary supplementation of l-arginine (l-Arg) on shock in severely burned patients. METHODS: This was a prospective, randomized, single blind, controlled study. Forty-seven severely burned patients due to various causes with a total burn surface area (TBSA) more than 50% each admitted in early postburn phase (within 10h postburn) were included in this study. All patients were treated by the traditional resuscitation program of our institute. After the nasogastric feeding tube was placed, they were randomly divided into three groups-(1) group A400 (n = 16): giving gastrointestinal feeding with 500 ml 5% GNS, containing l-Arg (400 mg/ kgday) at equal pace with fluid resuscitation; (2) group A200 (n = 16): giving gastrointestinal feeding with 500 ml 5% GNS containing l-Arg (200 mg/ kgday); (3) group C (n = 15): giving gastrointestinal feeding with 500 ml 5% GNS without any supplementation. The feeding started within 12h after burn and lasted for 72 h, the feeding rate was controlled by an enteral feeding pump. The following parameters were observed on days (PBD) 1-4: serum nitric oxide content (NO), mean arterial blood pressure (MAP), oxygenation index (PO2/FiO2), and arterial blood content of lactic acid (LA). Gastric mucosal blood flow was measured by laser Doppler flow-metry on PBD1 and PBD2. RESULTS: (1) Enteral feeding of l-Arg did not change MAP of severely burned patients, with no difference in MAP between the l-Arg supplemented and control groups. (2) There were significant changes of the l-Arg supplemented groups (A400 and A200), with an increased gastric mucosa blood flow, oxygenation index, and a decreased LA content in arterial blood, compared with the control group. (3) The serous NO content was significantly decreased in the A400 group on PBD2-4 (P < 0.01), and in the A200 group on PBD4 (P < 0.05) compared with the control group. CONCLUSIONS: Enteral feeding with l-arginine supplementation on early stage of burn decreases NO production to a relatively normal level and exerts beneficial effects on the resuscitation of burned shock.

Adolescent↗

A statistical method for chromatographic alignment of LC-MS data.

Integrated liquid-chromatography mass-spectrometry (LC-MS) is becoming a widely used approach for quantifying the protein composition of complex samples. The output of the LC-MS system measures the intensity of a peptide with a specific mass-charge ratio and retention time. In the last few years, this technology has been used to compare complex biological samples across multiple conditions. One challenge for comparative proteomic profiling with LC-MS is to match corresponding peptide features from different experiments. In this paper, we propose a new method--Peptide Element Alignment (PETAL) that uses raw spectrum data and detected peak to simultaneously align features from multiple LC-MS experiments. PETAL creates spectrum elements, each of which represents the mass spectrum of a single peptide in a single scan. Peptides detected in different LC-MS data are aligned if they can be represented by the same elements. By considering each peptide separately, PETAL enjoys greater flexibility than time warping methods. While most existing methods process multiple data sets by sequentially aligning each data set to an arbitrarily chosen template data set, PETAL treats all experiments symmetrically and can analyze all experiments simultaneously. We illustrate the performance of PETAL on example data sets.

Animals↗

A suite of algorithms for the comprehensive analysis of complex protein mixtures using high-resolution LC-MS.

MOTIVATION: Comparing two or more complex protein mixtures using liquid chromatography mass spectrometry (LC-MS) requires multiple analysis steps to locate and quantitate natural peptides within a single experiment and to align and normalize findings across multiple experiments. RESULTS: We describe msInspect, an open-source application comprising algorithms and visualization tools for the analysis of multiple LC-MS experimental measurements. The platform integrates novel algorithms for detecting signatures of natural peptides within a single LC-MS measurement and combines multiple experimental measurements into a peptide array, which may then be mined using analysis tools traditionally applied to genomic array analysis. The platform supports quantitation by both label-free and isotopic labeling approaches. The software implementation has been designed so that many key components may be easily replaced, making it useful as a workbench for integrating other novel algorithms developed by a growing research community. AVAILABILITY: The msInspect software is distributed freely under an Apache 2.0 license. The software as well as a Zip file with all peptide feature files and scripts needed to generate the tables and figures in this article are available at http://proteomics.fhcrc.org/.

Algorithms↗

Glutamine granule-supplemented enteral nutrition maintains immunological function in severely burned patients.

Glutamine is an important energy source for immune cells. It is a necessary nutrient for cell proliferation, and serves as specific fuel for lymphocytes, macrophages, and enterocytes when it is present in appropriate concentrations. The purpose of this clinical study was to observe the effects of enteral nutrition supplemented with glutamine granules on immunologic function in severely burned patients. Forty-eight severely burned patients (total burn surface area 30-75%, full thickness burn area 20-58%) who met the requirements of the protocol joined this double-blind randomized controlled clinical trail. Patients were randomly divided into two groups: burn control group (B group, 23 patients) and glutamine treated group (Gln group, 25 patients). There was isonitrogenous and isocaloric intake in both groups, Gln and B group patents were given glutamine granules or placebo (glycine) at 0.5 g/kgd for 14 days with oral feeding or tube feeding, respectively. The plasma level of glutamine and several indices of immunologic function including lymphocyte transformation ratio, neutrophil phagocytosis index (NPI), CD4/CD8 ratio, the content of immunoglobulin, complement C3, C4 and IL-2 levels were determined. Moreover, wound healing rate of burn area was observed and then hospital stay was recorded. The results showed significantly reduced plasma glutamine and damaged immunological function after severe burn Indices of cellular immunity function were remarkably decreased from normal controls. After taking glutamine granules for 14 days, plasma glutamine concentration was significantly higher in Gln group than that in B group (607.86+/-147.25 micromol/L versus 447.63+/-132.38 micromol/L, P<0.01). On the other hand, cellular immunity functions were improved in Gln group, such as lymphocyte transformation ratio, NPI, CD4/CD8 ratio and IL-2 compared those in the B group (P<0.05-0.01). However, for humoral immunity function such as the concentration of IgG, IgM, C3, C4, no marked changes were seen compared with the B group (P>0.05). In addition, wound healing was better and hospital stay days were reduced in Gln group (46.59+/-12.98 days versus 55.68+/-17.36 days, P<0.05). These indicated that immunological function damage is present after severe burn; supplemented glutamine granules with oral feeding or tube feeding abate the degree of immunosuppression, improve immunological function especially cellular immunity function, ameliorate wound healing and reduce hospital stay.

Adolescent↗

Reconstructing genetic ancestry blocks in admixed individuals.

A chromosome in an individual of recently admixed ancestry resembles a mosaic of chromosomal segments, or ancestry blocks, each derived from a particular ancestral population. We consider the problem of inferring ancestry along the chromosomes in an admixed individual and thereby delineating the ancestry blocks. Using a simple population model, we infer gene-flow history in each individual. Compared with existing methods, which are based on a hidden Markov model, the Markov-hidden Markov model (MHMM) we propose has the advantage of accounting for the background linkage disequilibrium (LD) that exists in ancestral populations. When there are more than two ancestral groups, we allow each ancestral population to admix at a different time in history. We use simulations to illustrate the accuracy of the inferred ancestry as well as the importance of modeling the background LD; not accounting for background LD between markers may mislead us to false inferences about mixed ancestry in an indigenous population. The MHMM makes it possible to identify genomic blocks of a particular ancestry by use of any high-density single-nucleotide-polymorphism panel. One application of our method is to perform admixture mapping without genotyping special ancestry-informative-marker panels.

Genetics, Medical↗

Neural expression of alpha-internexin promoter in vitro and in vivo.

alpha-Internexin is a 66 kDa neuronal intermediate filament protein found most abundantly in the neurons of the nervous systems during early development. To characterize the function of mouse alpha-internexin promoter, we designed two different expression constructs driven by 0.7 kb or 1.3 kb of mouse alpha-internexin 5'-flanking sequences; one was the enhanced green fluorescent protein (EGFP) reporter for monitoring specific expression in vitro, and the other was the cre for studying the functional DNA recombinase in transgenic mice. After introducing DNA constructs into non-neuronal 3T3 fibroblasts and a neuronal Neuro2A cell line by lipofectamine transfection, we observed that the expression of EGFP with 1.3 kb mouse alpha-internexin promoter was in a neuron-dominant manner. To establish a tissue-specific pattern in the nervous system, we generated a transgenic mouse line expressing Cre DNA recombinase under the control of 1.3 kb alpha-Internexin promoter. The activity of the Cre recombinase at postnatal day 1 was examined by mating the cre transgenic mice to ROSA26 reporter (R26R) mice with knock-in Cre-mediated recombination. Analyses of postnatal day 1 (P1) newborns showed that beta-galactosidase activity was detected in the peripheral nervous system (PNS), such as cranial nerves innervating the tongue and the skin as well as spinal nerves to the body trunk. Furthermore, X-gal-labeled dorsal root ganglionic (DRG) neurons showed positive for alpha-Internexin in cell bodies but negative in their spinal nerves. The motor neurons in the spinal cord did not exhibit any beta-galactosidase activity. Therefore, the cre transgene driven by mouse alpha-internexin promoter, described here, provides a useful animal model to specifically manipulate genes in the developing nervous system.

3T3 Cells↗

Differential label-free quantitative proteomic analysis of Shewanella oneidensis cultured under aerobic and suboxic conditions by accurate mass and time tag approach.

We describe the application of LC-MS without the use of stable isotope labeling for differential quantitative proteomic analysis of whole cell lysates of Shewanella oneidensis MR-1 cultured under aerobic and suboxic conditions. LC-MS/MS was used to initially identify peptide sequences, and LC-FTICR was used to confirm these identifications as well as measure relative peptide abundances. 2343 peptides covering 668 proteins were identified with high confidence and quantified. Among these proteins, a subset of 56 changed significantly using statistical approaches such as statistical analysis of microarrays, whereas another subset of 56 that were annotated as performing housekeeping functions remained essentially unchanged in relative abundance. Numerous proteins involved in anaerobic energy metabolism exhibited up to a 10-fold increase in relative abundance when S. oneidensis was transitioned from aerobic to suboxic conditions.

Amino Acid Sequence↗

Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer.

Breast cancer is a leading cause of cancer-death among women, where the clinicopathological features of tumors are used to prognosticate and guide therapy. DNA copy number alterations (CNAs), which occur frequently in breast cancer and define key pathogenetic events, are also potentially useful prognostic or predictive factors. Here, we report a genome-wide array-based comparative genomic hybridization (array CGH) survey of CNAs in 89 breast tumors from a patient cohort with locally advanced disease. Statistical analysis links distinct cytoband loci harboring CNAs to specific clinicopathological parameters, including tumor grade, estrogen receptor status, presence of TP53 mutation, and overall survival. Notably, distinct spectra of CNAs also underlie the different subtypes of breast cancer recently defined by expression-profiling, implying these subtypes develop along distinct genetic pathways. In addition, higher numbers of gains/losses are associated with the "basal-like" tumor subtype, while high-level DNA amplification is more frequent in "luminal-B" subtype tumors, suggesting also that distinct mechanisms of genomic instability might underlie their pathogenesis. The identified CNAs may provide a basis for improved patient prognostication, as well as a starting point to define important genes to further our understanding of the pathobiology of breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat

Breast Neoplasms↗

Quality control metrics for LC-MS feature detection tools demonstrated on Saccharomyces cerevisiae proteomic profiles.

Quantitative proteomic profiling using liquid chromatography-mass spectrometry is emerging as an important tool for biomarker discovery, prompting development of algorithms for high-throughput peptide feature detection in complex samples. However, neither annotated standard data sets nor quality control metrics currently exist for assessing the validity of feature detection algorithms. We propose a quality control metric, Mass Deviance, for assessing the accuracy of feature detection tools. Because the Mass Deviance metric is derived from the natural distribution of peptide masses, it is machine- and proteome-independent and enables assessment of feature detection tools in the absence of completely annotated data sets. We validate the use of Mass Deviance with a second, independent metric that is based on isotopic distributions, demonstrating that we can use Mass Deviance to identify aberrant features with high accuracy. We then demonstrate the use of independent metrics in tandem as a robust way to evaluate the performance of peptide feature detection algorithms. This work is done on complex LC-MS profiles of Saccharomyces cerevisiae which present a significant challenge to peptide feature detection algorithms.

Algorithms↗

No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m.

Koehle, Michael S., Pei Wang, Jordan A. Guenette, and Jim L. Rupert. No association between variants in the ACE and angiotensin II receptor 1 genes and acute mountain sickness in Nepalese pilgrims to the Janai Purnima Festival at 4380 m. High Alt. Med. Biol. 7:281-289, 2006.--Acute mountain sickness (AMS) causes significant morbidity among visitors to altitude. The primary contributors to developing AMS are altitude and rate of ascent; however, the substantial variation in susceptibility between individuals has led a number of investigators to propose that there may be genetic predilection to the disease. The ACE I/D polymorphism has been shown to predict performance among elite mountaineers. This study compares genotype and allele frequencies at the ACE I/D locus, two other loci in the ACE gene, and one locus in the angiotensin-2 receptor gene between individuals who did, or did not, express signs of AMS while attending a high altitude religious festival in Nepal (4380 m). Subjects (80 males, 23 females) were recruited and genotyped. All subjects were Nepalese. Forty-four of the subjects had been diagnosed with AMS by physicians at a high altitude health camp; the rest were free from altitude illness. All subjects were genotyped at polymorphic loci in the genes encoding angiotensin converting enzyme (ACE) and angiotensin II receptor type 1 gene (AGTR1). The polymorphisms examined were two single nucleotide polymorphisms (SNPs) in ACE (ACE(A-240T), dbSNP rs4291; and ACE(A2350G), dbSNP rs4343), the intronic Alu insertion in ACE (ACE I/D), and the SNP ATR(A1166C), (dbSNP rs17231380) in AGTR1d. All polymorphisms in ACE were found to be in linkage disequilibrium. No significant associations were found between AMS incidence and any of the alleles, suggesting that variants at these loci do not contribute to susceptibility to AMS in this population.

Acute Disease↗

[Identification of P. gingivalis P. intermedia P. nigrescens by 16S rDNA and membrane microarray chip].

PURPOSE: The aim of this study is to identify three kinds of black-pigmented periodontal pathogens P. gingivalis Pg, P. intermedia Pi, P. nigrescens Pn by 16S rDNA and microarray. METHODS: A pair of universal primers which can amplify a section of conservative domain of bacterial 16S rDNA based on the sequences of 16S rDNA in Genebank were designed. Then the specific oligonucleotide probes for Pg Pi Pn based on the sequences of the conservative domain were constructed. Standard bacterial genomic DNAs were amplified using the designed universal primers by PCR, and labeled by digoxigenin at the same time, the products of PCR were hybridized with the microarray in which the specific probes were added. The results of hybridization were analysed. RESULTS: The results of hybridization showed that the specific probes of Pg Pi Pn on microarray reacted only with corresponding PCR products of Pg Pi Pn, not reacted with others. CONCLUSION: The method of 16S rDNA and membrane microarray could be useful to identify Pg Pi Pn, and had high specificity. It will be developed into a kind of clinical bacterial detective system.

Comparative Genomic Hybridization↗