Biomedical subjects

Xiaowei Zhu

Publications and source records attributed to Xiaowei Zhu.

14 recordsLinked to original sources

PubMed2007

Comparison of Cobb angle measurement of scoliosis radiographs with preselected end vertebrae: traditional versus digital acquisition.

STUDY DESIGN: Prospective study. OBJECTIVE: To compare variability in Cobb angle between digitally and traditionally acquired scoliosis radiographs. SUMMARY OF BACKGROUND DATA: Previous studies have shown that the 95% confidence interval for Cobb angle can vary from 2.6 degrees to 8.8 degrees. No study directly comparing Cobb angles measured from traditional and digitally acquired radiographs has been reported. METHODS: A spine model simulating 25 single right thoracic curves (range, 20 degrees-60 degrees) was imaged using traditional and digital techniques. Traditional films and miniaturized printed digital films were each measured twice manually. Digital films were also measured twice using computer imaging software. RESULTS: Overall mean angle and (95% confidence interval) were 41.7 degrees (39.1 degrees-44.3 degrees) for traditional, 40.6 degrees (37.4 degrees-43.8 degrees) for digital, and 39.7 degrees (36.3 degrees-43.1 degrees) for computer measurements. Overall correlation was 0.994 for traditional and digital, 0.987 for traditional and computer, and 0.993 for digital and computer. Fixed effect model analysis demonstrated that, although a statistically significant difference existed between the 3 methods of measuring the Cobb angle (P < 0.0001), the difference between methods was less than 2 degrees. CONCLUSIONS: Any of the 3 evaluated methods of measurement can be used to measure Cobb angles. Additionally, the methods can be used interchangeably.

Image Interpretation, Computer-Assisted↗

PubMed2006

Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray.

To monitor severe acute respiratory syndrome (SARS) infection, a coronavirus protein microarray that harbors proteins from SARS coronavirus (SARS-CoV) and five additional coronaviruses was constructed. These microarrays were used to screen approximately 400 Canadian sera from the SARS outbreak, including samples from confirmed SARS-CoV cases, respiratory illness patients, and healthcare professionals. A computer algorithm that uses multiple classifiers to predict samples from SARS patients was developed and used to predict 206 sera from Chinese fever patients. The test assigned patients into two distinct groups: those with antibodies to SARS-CoV and those without. The microarray also identified patients with sera reactive against other coronavirus proteins. Our results correlated well with an indirect immunofluorescence test and demonstrated that viral infection can be monitored for many months after infection. We show that protein microarrays can serve as a rapid, sensitive, and simple tool for large-scale identification of viral-specific antibodies in sera.

Algorithms↗

PubMed2006

Extrapolating traditional DNA microarray statistics to tiling and protein microarray technologies.

A credit to microarray technology is its broad application. Two experiments--the tiling microarray experiment and the protein microarray experiment--are exemplars of the versatility of the microarrays. With the technology's expanding list of uses, the corresponding bioinformatics must evolve in step. There currently exists a rich literature developing statistical techniques for analyzing traditional gene-centric DNA microarrays, so the first challenge in analyzing the advanced technologies is to identify which of the existing statistical protocols are relevant and where and when revised methods are needed. A second challenge is making these often very technical ideas accessible to the broader microarray community. The aim of this chapter is to present some of the most widely used statistical techniques for normalizing and scoring traditional microarray data and indicate their potential utility for analyzing the newer protein and tiling microarray experiments. In so doing, we will assume little or no prior training in statistics of the reader. Areas covered include background correction, intensity normalization, spatial normalization, and the testing of statistical significance.

Animals↗

PubMed2006

ProCAT: a data analysis approach for protein microarrays.

Protein microarrays provide a versatile method for the analysis of many protein biochemical activities. Existing DNA microarray analytical methods do not translate to protein microarrays due to differences between the technologies. Here we report a new approach, ProCAT, which corrects for background bias and spatial artifacts, identifies significant signals, filters nonspecific spots, and normalizes the resulting signal to protein abundance. ProCAT provides a powerful and flexible new approach for analyzing many types of protein microarrays.

Cyclic AMP-Dependent Protein Kinases↗

PubMed2005

Global analysis of protein phosphorylation in yeast.

Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.

Eukaryotic Cells↗

PubMed2005

Effective radiation dose from radiologic studies in pediatric trauma patients.

Evaluation of the pediatric trauma patient frequently requires radiologic studies. Although low-dose radiation from diagnostic radiology is considered safe, lifetime risks per unit dose of radiation are increased in children compared to adults. The total effective dose of radiation to a typical pediatric trauma patient is unknown. We sought to estimate the total effective dose of radiation related to the radiologic assessment of injured children admitted to a pediatric Level I trauma center. We reviewed the radiology records of all children admitted directly to a trauma center in 2002 and tabulated all plain films, computed tomograms, angiographic/fluoroscopic studies, and nuclear medicine studies. Using age-adjusted effective doses (which incorporate biologic effects of radiation), we computed each patient's total effective dose of radiation. Of 506 admitted patients, 394 (78%) underwent at least one radiologic study. The mean total effective dose per patient was 14.9 mSv (median: 7.2 mSv; interquartile range: 2.2-27.4 mSv). On average, computed tomography accounted for 97.5% of total effective dose. Age and injury severity score did not predict total effective dose. We conclude that in pediatric trauma patients, the estimated total effective dose of radiation varied widely. Computed tomography contributed virtually the entire total effective dose. Regarding radiographic evaluation of pediatric trauma patients, the risks and benefits of current practices should continue to be evaluated critically, because lifetime risks associated with radiation exposure are inversely proportional to age at exposure.

Adolescent↗

PubMed2005

Global analysis of protein function using protein microarrays.

Protein microarrays containing thousands of proteins arrayed at high density can be prepared and probed for a wide variety of activities, thereby allowing the large scale analysis of many proteins simultaneously. In addition to identifying the activities of many previously uncharacterized proteins, protein microarrays can reveal new activities of well-characterized proteins, thus providing new insights about the functions of these proteins. Below, we describe the construction and use of protein microarrays and their applications using yeast as a model system.

Animals↗

PubMed2004

Global identification of human transcribed sequences with genome tiling arrays.

Elucidating the transcribed regions of the genome constitutes a fundamental aspect of human biology, yet this remains an outstanding problem. To comprehensively identify coding sequences, we constructed a series of high-density oligonucleotide tiling arrays representing sense and antisense strands of the entire nonrepetitive sequence of the human genome. Transcribed sequences were located across the genome via hybridization to complementary DNA samples, reverse-transcribed from polyadenylated RNA obtained from human liver tissue. In addition to identifying many known and predicted genes, we found 10,595 transcribed sequences not detected by other methods. A large fraction of these are located in intergenic regions distal from previously annotated genes and exhibit significant homology to other mammalian proteins.

Animals↗

PubMed2004

Regulation of gene expression by a metabolic enzyme.

Gene expression in eukaryotes is normally believed to be controlled by transcriptional regulators that activate genes encoding structural proteins and enzymes. To identify previously unrecognized DNA binding activities, a yeast proteome microarray was screened with DNA probes; Arg5,6, a well-characterized mitochondrial enzyme involved in arginine biosynthesis, was identified. Chromatin immunoprecipitation experiments revealed that Arg5,6 is associated with specific nuclear and mitochondrial loci in vivo, and Arg5,6 binds to specific fragments in vitro. Deletion of Arg5,6 causes altered transcript levels of both nuclear and mitochondrial target genes. These results indicate that metabolic enzymes can directly regulate eukaryotic gene expression.

Aldehyde Oxidoreductases↗

PubMed2004

TopNet: a tool for comparing biological sub-networks, correlating protein properties with topological statistics.

Biological networks are a topic of great current interest, particularly with the publication of a number of large genome-wide interaction datasets. They are globally characterized by a variety of graph-theoretic statistics, such as the degree distribution, clustering coefficient, characteristic path length and diameter. Moreover, real protein networks are quite complex and can often be divided into many sub-networks through systematic selection of different nodes and edges. For instance, proteins can be sub-divided by expression level, length, amino-acid composition, solubility, secondary structure and function. A challenging research question is to compare the topologies of sub- networks, looking for global differences associated with different types of proteins. TopNet is an automated web tool designed to address this question, calculating and comparing topological characteristics for different sub-networks derived from any given protein network. It provides reasonable solutions to the calculation of network statistics for sub-networks embedded within a larger network and gives simplified views of a sub-network of interest, allowing one to navigate through it. After constructing TopNet, we applied it to the interaction networks and protein classes currently available for yeast. We were able to find a number of potential biological correlations. In particular, we found that soluble proteins had more interactions than membrane proteins. Moreover, amongst soluble proteins, those that were highly expressed, had many polar amino acids, and had many alpha helices, tended to have the most interaction partners. Interestingly, TopNet also turned up some systematic biases in the current yeast interaction network: on average, proteins with a known functional classification had many more interaction partners than those without. This phenomenon may reflect the incompleteness of the experimentally determined yeast interaction network.

Algorithms↗

PubMed2004

Genomic analysis of essentiality within protein networks.

In this article, we introduce the notion of 'marginal essentiality' through combining quantitatively the results from large-scale phenotypic experiments (e.g. growth rate inhibition from knockouts). We find that this quantity relates to many of the topological characteristics of protein-protein interaction networks. In particular, proteins with a greater degree of marginal essentiality tend to be network hubs (i.e. with many interactions) and tend to have a shorter characteristic path length to their neighbors. We extend our network analysis to encompass transcriptional regulatory networks. Although transcription factors with many targets tend to be essential, surprisingly, we find that genes that are regulated by many transcription factors are usually not essential.

Animals↗

PubMed2004

Radiation safety considerations with yttrium 90 ibritumomab tiuxetan (Zevalin).

Radioimmunotherapy is a recently approved treatment modality for non-Hodgkin's lymphoma that enables physicians to target cytotoxic localized radiation to tumor sites without using external-beam sources. Because it uses a pure beta emitter for therapy, (90)Y ibritumomab tiuxetan can be safely and routinely administered in an outpatient procedure, with few discharge instructions, and minimal risk of radiation exposure to a patient's family and acquaintances. Safety precautions for medical professionals administering (90)Y ibritumomab tiuxetan are universal precautions, with the addition of acrylic shielding for the administration of radiolabeled doses. The risk of radiation exposure to healthcare workers and family members is minimal. The primary route for biologic elimination of (90)Y ibritumomab tiuxetan is through the urine. While radiation safety instructions are not required according to the relevant patient release criteria, basic instructions to the patient and family may be valuable to further minimize the risk of radiation exposure and help alleviate patient and family concerns.

Antibodies, Monoclonal↗

PubMed2004

Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs.

Proteins function mainly through interactions, especially with DNA and other proteins. While some large-scale interaction networks are now available for a number of model organisms, their experimental generation remains difficult. Consequently, interolog mapping--the transfer of interaction annotation from one organism to another using comparative genomics--is of significant value. Here we quantitatively assess the degree to which interologs can be reliably transferred between species as a function of the sequence similarity of the corresponding interacting proteins. Using interaction information from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Helicobacter pylori, we find that protein-protein interactions can be transferred when a pair of proteins has a joint sequence identity >80% or a joint E-value <10(-70). (These "joint" quantities are the geometric means of the identities or E-values for the two pairs of interacting proteins.) We generalize our interolog analysis to protein-DNA binding, finding such interactions are conserved at specific thresholds between 30% and 60% sequence identity depending on the protein family. Furthermore, we introduce the concept of a "regulog"--a conserved regulatory relationship between proteins across different species. We map interologs and regulogs from yeast to a number of genomes with limited experimental annotation (e.g., Arabidopsis thaliana) and make these available through an online database at http://interolog.gersteinlab.org. Specifically, we are able to transfer approximately 90,000 potential protein-protein interactions to the worm. We test a number of these in two-hybrid experiments and are able to verify 45 overlaps, which we show to be statistically significant.

Amino Acid Sequence↗

PubMed2003

Radiation safety considerations with therapeutic 90Y Zevalin.

ABSTRACT Radioimmunotherapy with the 90Y-labeled Zevalin radioimmunoconjugate is a new and promising modality in cancer treatment that combines the targeting power of monoclonal antibodies with the cytotoxicity of localized radiation. 90Y is a pure beta emitter, with different physical characteristics than traditional therapeutic radionuclides such as 131I. It is important that radiation safety professionals understand the characteristics of this radionuclide so that effective radiation safety procedures can be implemented with the Zevalin regimen. Because 90Y is a pure beta emitter, the Zevalin regimen is routinely administered as an outpatient procedure and is administered by using plastic shielding. Once the radioimmunoconjugate has been administered, the risk of radiation exposure to healthcare workers and family members is minimal. The primary route of biologic elimination of 90Y Zevalin is through the urinary system, with approximately 7% of the total activity administered eliminated over the course of 1 wk. Standard universal precautions, which should already be in place in healthcare facilities, should be sufficient to prevent radiation exposure to personnel working with patients who have been treated with Zevalin. Written radiation safety instructions for patients are not required, but basic instructions to the patient and his or her family may help further minimize the risk of radiation exposure and help alleviate patient and family concerns.

Antibodies, Monoclonal↗