Biomedical subjects

Xiaolin Wu

Publications and source records attributed to Xiaolin Wu.

At least 19 recordsLinked to original sources

PubMed2026

Identification of elements determining KIR gene demethylation at the CD56-bright stage of NK cell development.

The variegated expression of the KIR family of class I MHC receptors generates specialized natural killer (NK) cells capable of allele-specific HLA recognition. Understanding the mechanism of KIR gene activation will lead to improved methods for the generation of fully functional NK cells. A central RUNX-binding site in the KIR proximal promoter is required for gene activation. RUNX proteins recruit ten-eleven translocation (TET) proteins that generate 5-hydroxymethylcytosine (5hmC) and drive DNA demethylation. Assessment of 5-methylcytosine (5mC) and 5hmC residues at four stages of NK cell development reveals deposition of 5hmC primarily in a CREB site next to the RUNX site at the CD56Bright stage but not the subsequent CD56Dim stage representing fully mature NK cells. KIR promoter demethylation is delayed relative to other lineage-associated genes, indicating a high threshold for KIR gene demethylation in developing NK cells, and a window of opportunity for RUNX/TET-dependent KIR gene activation in CD56Bright NK cells.

6-base sequencing↗

PubMed2006

GEL: a novel genotype calling algorithm using empirical likelihood.

MOTIVATION: Preliminary results on the data produced using the Affymetrix large-scale genotyping platforms show that it is necessary to construct improved genotype calling algorithms. There is evidence that some of the existing algorithms lead to an increased error rate in heterozygous genotypes, and a disproportionately large rate of heterozygotes with missing genotypes. Non-random errors and missing data can lead to an increase in the number of false discoveries in genetic association studies. Therefore, the factors that need to be evaluated in assessing the performance of an algorithm are the missing data (call) and error rates, but also the heterozygous proportions in missing data and errors. RESULTS: We introduce a novel genotype calling algorithm (GEL) for the Affymetrix GeneChip arrays. The algorithm uses likelihood calculations that are based on distributions inferred from the observed data. A key ingredient in accurate genotype calling is weighting the information that comes from each probe quartet according to the quality/reliability of the data in the quartet, and prior information on the performance of the quartet. AVAILABILITY: The GEL software is implemented in R and is available by request from the corresponding author at nicolae@galton.uchicago.edu.

Algorithms↗

PubMed2006

New complexities in the genetics of stuttering: significant sex-specific linkage signals.

Stuttering is a speech disorder long recognized to have a genetic component. Recent linkage studies mapped a susceptibility locus for stuttering to chromosome 12 in 46 highly inbred families ascertained in Pakistan. We report here on linkage studies in 100 families of European descent ascertained in the United States, Sweden, and Israel. These families included 252 individuals exhibiting persistent stuttering, 45 individuals classified as recovered from stuttering, and 19 individuals too young to classify. Primary analyses identified moderate evidence for linkage of the broader diagnosis of "ever stuttered" (including both persistent and recovered stuttering) on chromosome 9 (LOD = 2.3 at 60 cM) and of the narrower diagnosis of persistent stuttering on chromosome 15 (LOD = 1.95 at 23 cM). In contrast, sex-specific evidence for linkage on chromosome 7 at 153 cM in the male-only data subset (LOD = 2.99) and on chromosome 21 at 34 cM in the female-only data subset (LOD = 4.5) met genomewide criteria for significance. Secondary analyses revealed a significant increase in the evidence for linkage on chromosome 12, conditional on the evidence for linkage at chromosome 7, with the location of the increased signal congruent with the previously reported signal in families ascertained in Pakistan. In addition, a region on chromosome 2 (193 cM) showed a significant increase in the evidence for linkage conditional on either chromosome 9 (positive) or chromosome 7 (negative); this chromosome 2 region has been implicated elsewhere in studies on autism, with increased evidence for linkage observed when the sample is restricted to those with delayed onset of phrase speech. Our results support the hypothesis that the genetic component to stuttering has significant sex effects.

Chromosome Mapping↗

PubMed2006

Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder.

CONTEXT: The first 2 independent linkage studies for obsessive-compulsive disorder (OCD) identified a region on 9p24 with suggestive evidence for linkage. The glutamate transporter gene solute carrier family 1, member 1 (SLC1A1) is a promising functional candidate in this region because altered glutamatergic concentrations have been found in the striatum and anterior cingulate in neuroimaging studies of pediatric OCD. OBJECTIVE: To determine whether genotypes at polymorphisms in the SLC1A1 gene region are associated with early-onset OCD. DESIGN: Family-based analysis of association using the transmission disequilibrium test, confirmed using the family-based association test. SETTING: Anxiety disorders program in an academic medical center. PARTICIPANTS: Seventy-one probands with DSM-III-R or DSM-IV OCD and their parents. METHODS: Nine single nucleotide polymorphisms spaced throughout the SLC1A1 gene region were genotyped. RESULTS: Significant association was detected at rs3780412 (P = .04) and rs301430 (P = .03), 2 common adjacent single nucleotide polymorphisms in the 3' region of SLC1A1. Analysis by sex revealed that association at rs3780412 was limited to male probands (P = .002). Significant association was also detected for the T/C haplotype at rs301430-rs301979 (P = .03), the only haplotype block identified among the 9 single nucleotide polymorphisms. Analysis by sex also revealed that the haplotype association was limited to male probands (P = .003). A deletion in the 3' flanking region of SLC1A1 was also detected that imperfectly segregated with OCD in a large, multigenerational family with multiple affected individuals. CONCLUSIONS: The 3' region of SLC1A1 may contain a susceptibility allele for early-onset OCD, with differential effects in males and females. The results also provide further support for the involvement of a glutamatergic dysfunction in the pathogenesis of early-onset OCD.

Adolescent↗

PubMed2006

Context quantization by kernel Fisher discriminant.

Optimal context quantizers for minimum conditional entropy can be constructed by dynamic programming in the probability simplex space. The main difficulty, operationally, is the resulting complex quantizer mapping function in the context space, in which the conditional entropy coding is conducted. To overcome this difficulty, we propose new algorithms for designing context quantizers in the context space based on the multiclass Fisher discriminant and the kernel Fisher discriminant (KFD). In particular, the KFD can describe linearly nonseparable quantizer cells by projecting input context vectors onto a high-dimensional curve, in which these cells become better separable. The new algorithms outperform the previous linear Fisher discriminant method for context quantization. They approach the minimum empirical conditional entropy context quantizer designed in the probability simplex space, but with a practical implementation that employs a simple scalar quantizer mapping function rather than a large lookup table.

Algorithms↗

PubMed2006

Lossless compression of color mosaic images.

Lossless compression of color mosaic images poses a unique and interesting problem of spectral decorrelation of spatially interleaved R, G, B samples. We investigate reversible lossless spectral-spatial transforms that can remove statistical redundancies in both spectral and spatial domains and discover that a particular wavelet decomposition scheme, called Mallat wavelet packet transform, is ideally suited to the task of decorrelating color mosaic data. We also propose a low-complexity adaptive context-based Golomb-Rice coding technique to compress the coefficients of Mallat wavelet packet transform. The lossless compression performance of the proposed method on color mosaic images is apparently the best so far among the existing lossless image codecs.

Algorithms↗

PubMed2006

An edge-guided image interpolation algorithm via directional filtering and data fusion.

Preserving edge structures is a challenge to image interpolation algorithms that reconstruct a high-resolution image from a low-resolution counterpart. We propose a new edge-guided nonlinear interpolation technique through directional filtering and data fusion. For a pixel to be interpolated, two observation sets are defined in two orthogonal directions, and each set produces an estimate of the pixel value. These directional estimates, modeled as different noisy measurements of the missing pixel are fused by the linear minimum mean square-error estimation (LMMSE) technique into a more robust estimate, using the statistics of the two observation sets. We also present a simplified version of the LMMSE-based interpolation algorithm to reduce computational cost without sacrificing much the interpolation performance. Experiments show that the new interpolation techniques can preserve edge sharpness and reduce ringing artifacts.

Algorithms↗

PubMed2006

Improvement of color video demosaicking in temporal domain.

Color demosaicking is critical to the image quality of digital still and video cameras that use a single-sensor array. Limited by the mosaic sampling pattern of the color filter array (CFA), color artifacts may occur in a demosaicked image in areas of high-frequency and/or sharp color transition structures. However, a color digital video camera captures a sequence of mosaic images and the temporal dimension of the color signals provides a rich source of information about the scene via camera and object motions. This paper proposes an inter-frame demosaicking approach to take advantage of all three forms of pixel correlations: spatial, spectral, and temporal. By motion estimation and statistical data fusion between adjacent mosaic frames, the new approach can remove much of the color artifacts that survive intra-frame demosaicking and also improve tone reproduction accuracy. Empirical results show that the proposed inter-frame demosaicking approach consistently outperforms its intra-frame counterparts both in peak signal-to-noise measure and subjective visual quality.

Algorithms↗

PubMed2006

EasyExonPrimer: automated primer design for exon sequences.

UNLABELLED: EasyExonPrimer is a web-based software that automates the design of PCR primers to amplify exon sequences from genomic DNA. EasyExonPrimer is written in Perl and uses Primer3 to design PCR primers based on the genome builds and annotation databases available at the University of California, Santa Cruz (UCSC) Genome Browser database (http://genome.ucsc.edu/). It masks repeats and known single nucleotide polymorphism (SNP) sites in the genome and designs standardised primers using optimised conditions. Users can input genes by RefSeq mRNA ID, gene name or keyword. The primer design is optimised for large-scale resequencing of exons. For exons larger than 1 kb, the user has the option of breaking the exon sequence down into overlapping smaller fragments. All primer pairs are then verified using the In-Silico PCR software to test for uniqueness in the genome. We have designed >1000 pairs of primers for 90 genes; 95% of the primer pairs successfully amplified exon sequences under standard PCR conditions without requiring further optimisation. AVAILABILITY: EasyExonPrimer is available from http://129.43.22.27/~primer/. The source code is also available upon request. CONTACT: Xiaolin Wu (forestwu@mail.nih.gov).

Algorithms↗

PubMed2006

WebaCGH: an interactive online tool for the analysis and display of array comparative genomic hybridisation data.

UNLABELLED: Gene copy number variations occur both in normal cells and in numerous pathologies including cancer and developmental diseases. Array comparative genomic hybridisation (aCGH) is an emerging technology that allows detection of chromosomal gains and losses in a high-resolution format. When aCGH is performed on cDNA and oligonucleotide microarrays, the impact of DNA copy number on gene transcription profiles may be directly compared. We have created an online software tool, WebaCGH, that functions to (i) upload aCGH and gene transcription results from multiple experiments; (ii) identify significant aberrant regions using a local Z-score threshold in user-selected chromosomal segments subjected to smoothing with moving averages; and (iii) display results in a graphical format with full genome and individual chromosome views. In the individual chromosome display, data can be zoomed in/out in both dimensions (i.e. ratio and physical location) and plotted features can have 'mouse over' linking to outside databases to identify loci of interest. Uploaded data can be stored indefinitely for subsequent retrieval and analysis. WebaCGH was created as a Java-based web application using the open-source database MySQL. AVAILABILITY: WebaCGH is freely accessible at http://129.43.22.27/WebaCGH/welcome.htm CONTACT: Xiaolin Wu (forestwu@mail.nih.gov) or Ulises Urzúa (uurzua@med.uchile.cl).

Animals↗

PubMed2005

Redefining the common insertion site.

Retroviral mutagenesis has been used as a powerful tool to discover genes involved in oncogenesis through a technique called Common Insertion Site (CIS) analysis where tumors are induced by proviral integrations and the genomic loci of the proviruses are identified. A fundamental assumption made in this analysis is that multiple proviral insertions in close proximity occurring more frequently than would be predicted randomly provides evidence that the genes near the integrations are involved in the formation of the tumors. We demonstrate here using data derived from MLV integrations not put under selection for tumor induction that CIS analysis as currently defined is often not a sufficient argument for a gene's significance in tumorigenesis.

Gene Expression Regulation↗

PubMed2005

Preferential selection of human T-cell leukemia virus type I provirus integration sites in leukemic versus carrier states.

Human T-cell leukemia virus type I (HTLV-I) is a causative agent of neoplastic disease, adult T-cell leukemia (ATL). Although the encoding viral proteins play an important role in oncogenesis, the role of the HTLV-I proviral integration site remains unsolved. We determined the integration sites of HTLV-I proviruses in ATL cells and HTLV-I-infected cells in asymptomatic carriers. In carrier and ATL cells, HTLV-I provirus was integrated into the transcriptional unit at frequencies of 26.8% (15/56) and 33.9% (20/59), respectively, which were equivalent to the frequency calculated based on random integration (33.2%). In addition, HTLV-I provirus was prone to integration near the transcriptional start sites in leukemic cells (P = .006), and the transcriptional direction of the provirus was in accordance with that of integrated cellular genes in 70% of cases. More importantly, the integration sites in the carrier cells favored the alphoid repetitive sequences (11/56; 20%) whereas in leukemic cells they disfavored these sequences (2/59; 3.4%). Taken together, during natural course from carrier to onset of ATL, HTLV-I-infected cells with integration sites favorable for viral gene transcription are susceptible to malignant transformation due to increased viral gene expression.

Base Sequence↗

PubMed2005

A comprehensive SNP-based genetic analysis of inbred mouse strains.

Dense genetic maps of mammalian genomes facilitate a variety of biological studies including the mapping of polygenic traits, positional cloning of monogenic traits, mapping of quantitative or qualitative trait loci, marker association, allelic imbalance, speed congenic construction, and evolutionary or phylogenetic comparison. In particular, single nucleotide polymorphisms (SNPs) have proved useful because of their abundance and compatibility with multiple high-throughput technology platforms. SNP genotyping is especially suited for the genetic analysis of model organisms such as the mouse because biallelic markers remain fully informative when used to characterize crosses between inbred strains. Here we report the mapping and genotyping of 673 SNPs (including 519 novel SNPs) in 55 of the most commonly used mouse strains. These data have allowed us to construct a phylogenetic tree that correlates and expands known genealogical relationships and clarifies the origin of strains previously having an uncertain ancestry. All 55 inbred strains are distinguishable genetically using this SNP panel. Our data reveal an uneven SNP distribution consistent with a mosaic pattern of inheritance and provide some insight into the changing dynamics of the physical architecture of the genome. Furthermore, these data represent a valuable resource for the selection of markers and the design of experiments that require the genetic distinction of any pair of mouse inbred strains such as the generation of congenic mice, positional cloning, and the mapping of quantitative or qualitative trait loci.

Animals↗

PubMed2005

Color demosaicking via directional linear minimum mean square-error estimation.

Digital cameras sample scenes using a color filter array of mosaic pattern (e.g., the Bayer pattern). The demosaicking of the color samples is critical to the image quality. This paper presents a new color demosaicking technique of optimal directional filtering of the green-red and green-blue difference signals. Under the assumption that the primary difference signals (PDS) between the green and red/blue channels are low pass, the missing green samples are adaptively estimated in both horizontal and vertical directions by the linear minimum mean square-error estimation (LMMSE) technique. These directional estimates are then optimally fused to further improve the green estimates. Finally, guided by the demosaicked full-resolution green channel, the other two color channels are reconstructed from the LMMSE filtered and fused PDS. The experimental results show that the presented color demosaicking technique outperforms the existing methods both in PSNR measure and visual perception.

Algorithms↗

PubMed2005

On multirate optimality of JPEG2000 code stream.

Arguably, the most important and defining feature of the JPEG2000 image compression standard is its R-D optimized code stream of multiple progressive layers. This code stream is an interleaving of many scalable code streams of different sample blocks. In this paper, we reexamine the R-D optimality of JPEG2000 scalable code streams under an expected multirate distortion measure (EMRD), which is defined to be the average distortion weighted by a probability distribution of operational rates in a given range, rather than for one or few fixed rates. We prove that the JPEG2000 code stream constructed by embedded block coding of optimal truncation is almost optimal in the EMRD sense for uniform rate distribution function, even if the individual scalable code streams have nonconvex operational R-D curves. We also develop algorithms to optimize the JPEG2000 code stream for exponential and Laplacian rate distribution functions while maintaining compatibility with the JPEG2000 standard. Both of our analytical and experimental results lend strong support to JPEG2000 as a near-optimal scalable image codec in a fairly general setting.

Algorithms↗

PubMed2005

Wavelet coding of volumetric medical images for high throughput and operability.

This paper presents a new three-dimensional (3-D) wavelet-based scalable lossless coding scheme for compression of volumetric medical images. Aiming to improve the productivity of radiologists and the cost-effectiveness of the system, we strive to achieve high decoder throughput, random access to coded data volume, progressive transmission, and high compression ratio in a balanced design approach. These desirable functionalities are realized by a modified 3-D dyadic wavelet transform tailored to volumetric medical images and an optimized Rice code of very low complexity.

Algorithms↗

PubMed2005

Canny edge detection enhancement by scale multiplication.

The technique of scale multiplication is analyzed in the framework of Canny edge detection. A scale multiplication function is defined as the product of the responses of the detection filter at two scales. Edge maps are constructed as the local maxima by thresholding the scale multiplication results. The detection and localization criteria of the scale multiplication are derived. At a small loss in the detection criterion, the localization criterion can be much improved by scale multiplication. The product of the two criteria for scale multiplication is greater than that for a single scale, which leads to better edge detection performance. Experimental results are presented.

Algorithms↗

PubMed2005

Simian immunodeficiency virus integration preference is similar to that of human immunodeficiency virus type 1.

Simian immunodeficiency virus (SIV) is a useful model for studying human immunodeficiency virus (HIV) pathogenesis and vaccine efficacy. As with all other retroviruses, integration is a necessary step in the replication cycle of SIV. The location of the retrovirus integration site is known to impact on viral gene expression, establishment of viral latency, and other aspects of the replication cycle of a retrovirus. In this study, 148 SIV provirus integration sites were sequenced and mapped in the human genome. Our analysis showed that SIV integration, like that of HIV type 1 (HIV-1), exhibited a strong preference for actively transcribed regions in the genome (A. R. Schroder et al., Cell 110:521-529, 2002) and no preference for the CpG islands or transcription start sites, in contrast to observations for murine leukemia virus (X. Wu et al., Science 300:1749-1751, 2003). The parallel integration target site preferences of SIV and HIV-1 suggest that these lentiviruses may share similar mechanisms for target site selection and that SIV serves as an accurate model of HIV-1 with respect to integration.

Cell Line↗