Publications by authors named "Zhiping Gu"

17 Publications

  • Page 1 of 1

Identification of a novel TP63 mutation causing nonsyndromic cleft lip with or without cleft palate.

BMC Med Genomics 2021 Feb 23;14(1):53. Epub 2021 Feb 23.

Department of Medical Genetics and Prenatal Diagnosis, Hospital Affiliated 5 to Nantong University (Taizhou People's Hospital), Taizhou, Jiangsu, China.

Background: Cleft lip with or without cleft palate (CL/P) is the most common craniofacial anomaly with a high incidence of live births. The specific pathogenesis of CL/P is still unclear, although plenty of studies have been conducted. Variations of tumor protein 63 (TP63) was reported to be related to the phenotype of CL/P. The case discussed in this report involves a pedigree with mutation at TP63 gene, and the variation was not reported before.

Case Presentation: A Chinese pedigree with CL/P was collected in this study. The proband is a 3-year-old boy with the phenotype of CL/P, while his global development and intelligence are normal. After two CL/P repair operations, he looks almost normal. The proband's uncle and grandmother both have the phenotype of CL/P. Cytogenetic analysis and chromosomal microarray analysis (CMA) were performed, followed by whole exome sequencing (WES) and sanger validation. Analysis of WES revealed a variant of C>T at nucleotide position 1324 (1324C>T) of TP63 gene, possibly producing a truncated protein with a premature stop codon at amino acid position 442 (p.Q442*). This mutation was localized at the oligomerization domain (OD) of TP63 and might impair the capacity of p63 oligomerization.

Conclusion: The mutation in TP63 was recognized to be the possible cause of the phenotype of CL/P in this pedigree. This report provides some evidence for the clinical diagnosis of CL/P. And our study also provides clinical evidence for the molecular mechanism of TP63 gene causing nonsyndromic cleft lip with or without cleft palate (NSCL/P).
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http://dx.doi.org/10.1186/s12920-021-00903-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903685PMC
February 2021

Enoxacin inhibits proliferation and invasion of human osteosarcoma cells and reduces bone tumour volume in a murine xenograft model.

Oncol Lett 2020 Aug 21;20(2):1400-1408. Epub 2020 May 21.

Department of Orthopaedics, The First Affiliated Hospital of Nanchang University, Artificial Joints Engineering and Technology Research Centre of Jiangxi Province, Nanchang, Jiangxi 330006, P.R. China.

Osteosarcoma is the most prevalent primary bone malignancy in children and adolescents. Neoadjuvant chemotherapy combined with surgical resection, the current standard treatment of osteosarcoma, is associated with a 5-year survival rate of only ~70%. Therefore, it is necessary to identify new, more effective treatment strategies for patients with this lethal disease. Enoxacin is a highly effective broad-spectrum fluoroquinolone antibiotic with low toxicity. The drug inhibits the growth and metastasis of numerous tumour types, but its efficacy has not been studied in osteosarcoma. This study assessed the antitumour effects of enoxacin in osteosarcoma 143B cells and in a murine tumour xenograft model. Enoxacin inhibited the proliferation, invasion and migration of 143B cells, as well as inducing their apoptosis. These effects were thought to be mediated by downregulation of Bcl-xL, Bxl-2, matrix metalloproteinase (MMP)2 and MMP9 expression. Enoxacin also significantly impaired the growth of bone tumours in nude mice without affecting their liver or kidney function, or blood cell count. Collectively, these results indicate that enoxacin is a promising new drug for osteosarcoma that warrants further evaluation in clinical studies.
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http://dx.doi.org/10.3892/ol.2020.11656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377056PMC
August 2020

Comparison between minimally invasive plate osteosynthesis and open reduction-internal fixation for proximal humeral fractures: a meta-analysis based on 1050 individuals.

BMC Musculoskelet Disord 2019 Nov 18;20(1):550. Epub 2019 Nov 18.

Department of Orthopedics, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Background: This meta-analysis aimed to compare the clinical outcomes and complications of minimally invasive plate osteosynthesis (MIPO) and open reduction-internal fixation (ORIF) in patients with proximal humeral fractures.

Methods: We searched PubMed, EMBASE, Ovid, and the Cochrane Library to identify all relevant studies from inception to April 2019. Cochrane Collaboration's Review Manage 5.3 was used for meta-analysis.

Results: Sixteen studies involving 1050 patients (464 patients in the MIPO group and 586 patients in the ORIF group) were finally included. According to the meta-analysis, MIPO was superior to ORIF in operation time, blood loss, postoperative pain, fracture union time, and constant score. However, MIPO was associated with more exposure to radiation and axillary nerve injury. No significant differences were found in length of hospital stays and complication except for axillary nerve injury.

Conclusion: The present evidence indicates that compared to ORIF, MIPO had advantages in functional outcomes, operation time, blood loss, postoperative pain, and fracture union time for the treatment of PHFs. However, the MIPO technique had a higher rate of axillary nerve injury and longer radiation time compared to ORIF.
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http://dx.doi.org/10.1186/s12891-019-2936-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862799PMC
November 2019

PDX-MI: Minimal Information for Patient-Derived Tumor Xenograft Models.

Cancer Res 2017 11;77(21):e62-e66

Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Patient-derived tumor xenograft (PDX) mouse models have emerged as an important oncology research platform to study tumor evolution, mechanisms of drug response and resistance, and tailoring chemotherapeutic approaches for individual patients. The lack of robust standards for reporting on PDX models has hampered the ability of researchers to find relevant PDX models and associated data. Here we present the PDX models minimal information standard (PDX-MI) for reporting on the generation, quality assurance, and use of PDX models. PDX-MI defines the minimal information for describing the clinical attributes of a patient's tumor, the processes of implantation and passaging of tumors in a host mouse strain, quality assurance methods, and the use of PDX models in cancer research. Adherence to PDX-MI standards will facilitate accurate search results for oncology models and their associated data across distributed repository databases and promote reproducibility in research studies using these models. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-0582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738926PMC
November 2017

Genetic changes found in a distinct clade of Enterovirus D68 associated with paralysis during the 2014 outbreak.

Virus Evol 2016 Jan 15;2(1):vew015. Epub 2016 Jun 15.

J. Craig Venter Institute, La Jolla, CA, USA.

Enterovirus D68 (EV-D68) caused a severe respiratory illness outbreak in the United States in 2014. Reports of acute flaccid myelitis (AFM)/paralysis (AFP) in several independent epidemiological clusters of children with detectable EV-D68 have raised concerns that genetic changes in EV-D68 could be causing increased disease severity and neurological symptoms. To explore the potential link between EV-D68 genetic variations and symptom changes, we performed a series of comparative genomic analyses of EV-D68 2014 outbreak isolate sequences using data and analytical tools in the Virus Pathogen Resource (ViPR; www.viprbrc.org). Our results suggest that (1) three distinct lineages of EV-D68 were co-circulating in 2013 and 2014; (2) isolates associated with AFM/AFP belong to a single phylogenetic subclade - B1; (3) the majority of isolates from the B1 subclade have 21 unique substitutions that distinguish them from other isolates, including amino acid substitutions in the VP1, VP2, and VP3 capsid proteins and the 3D RNA-dependent RNA polymerase, and nucleotide substitutions in the internal ribosome entry sequence (IRES); (4) at 12 of these positions, B1 isolates carry the same residues observed at equivalent positions in paralysis-causing enteroviruses, including poliovirus, EV-D70 and EV-A71. Based on these results, we hypothesize that unique B1 substitutions may be responsible for the apparent increased incidence of neuropathology associated with the 2014 outbreak.
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http://dx.doi.org/10.1093/ve/vew015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426007PMC
January 2016

Influenza Research Database: An integrated bioinformatics resource for influenza virus research.

Nucleic Acids Res 2017 01 26;45(D1):D466-D474. Epub 2016 Sep 26.

J. Craig Venter Institute, La Jolla, CA 92037, USA

The Influenza Research Database (IRD) is a U.S. National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Bioinformatics Resource Center dedicated to providing bioinformatics support for influenza virus research. IRD facilitates the research and development of vaccines, diagnostics and therapeutics against influenza virus by providing a comprehensive collection of influenza-related data integrated from various sources, a growing suite of analysis and visualization tools for data mining and hypothesis generation, personal workbench spaces for data storage and sharing, and active user community support. Here, we describe the recent improvements in IRD including the use of cloud and high performance computing resources, analysis and visualization of user-provided sequence data with associated metadata, predictions of novel variant proteins, annotations of phenotype-associated sequence markers and their predicted phenotypic effects, hemagglutinin (HA) clade classifications, an automated tool for HA subtype numbering conversion, linkouts to disease event data and the addition of host factor and antiviral drug components. All data and tools are freely available without restriction from the IRD website at https://www.fludb.org.
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http://dx.doi.org/10.1093/nar/gkw857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210613PMC
January 2017

Virus pathogen database and analysis resource (ViPR): a comprehensive bioinformatics database and analysis resource for the coronavirus research community.

Viruses 2012 Nov 19;4(11):3209-26. Epub 2012 Nov 19.

J. Craig Venter Institute, 10355 Science Center Dr., San Diego, CA 92121, USA.

Several viruses within the Coronaviridae family have been categorized as either emerging or re-emerging human pathogens, with Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) being the most well known. The NIAID-sponsored Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org) supports bioinformatics workflows for a broad range of human virus pathogens and other related viruses, including the entire Coronaviridae family. ViPR provides access to sequence records, gene and protein annotations, immune epitopes, 3D structures, host factor data, and other data types through an intuitive web-based search interface. Records returned from these queries can then be subjected to web-based analyses including: multiple sequence alignment, phylogenetic inference, sequence variation determination, BLAST comparison, and metadata-driven comparative genomics statistical analysis. Additional tools exist to display multiple sequence alignments, view phylogenetic trees, visualize 3D protein structures, transfer existing reference genome annotations to new genomes, and store or share results from any search or analysis within personal private 'Workbench' spaces for future access. All of the data and integrated analysis and visualization tools in ViPR are made available without charge as a service to the Coronaviridae research community to facilitate the research and development of diagnostics, prophylactics, vaccines and therapeutics against these human pathogens.
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http://dx.doi.org/10.3390/v4113209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509690PMC
November 2012

ViPR: an open bioinformatics database and analysis resource for virology research.

Nucleic Acids Res 2012 Jan 17;40(Database issue):D593-8. Epub 2011 Oct 17.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

The Virus Pathogen Database and Analysis Resource (ViPR, www.ViPRbrc.org) is an integrated repository of data and analysis tools for multiple virus families, supported by the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers (BRC) program. ViPR contains information for human pathogenic viruses belonging to the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Filoviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Picornaviridae, Poxviridae, Reoviridae, Rhabdoviridae and Togaviridae families, with plans to support additional virus families in the future. ViPR captures various types of information, including sequence records, gene and protein annotations, 3D protein structures, immune epitope locations, clinical and surveillance metadata and novel data derived from comparative genomics analysis. Analytical and visualization tools for metadata-driven statistical sequence analysis, multiple sequence alignment, phylogenetic tree construction, BLAST comparison and sequence variation determination are also provided. Data filtering and analysis workflows can be combined and the results saved in personal 'Workbenches' for future use. ViPR tools and data are available without charge as a service to the virology research community to help facilitate the development of diagnostics, prophylactics and therapeutics for priority pathogens and other viruses.
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http://dx.doi.org/10.1093/nar/gkr859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245011PMC
January 2012

Population genetic analysis of shotgun assemblies of genomic sequences from multiple individuals.

Genome Res 2008 Jul 14;18(7):1020-9. Epub 2008 Apr 14.

Departments of Integrative Biology and Statistics, University of California, Berkeley, California 94720, USA.

We introduce a simple, broadly applicable method for obtaining estimates of nucleotide diversity from genomic shotgun sequencing data. The method takes into account the special nature of these data: random sampling of genomic segments from one or more individuals and a relatively high error rate for individual reads. Applying this method to data from the Celera human genome sequencing and SNP discovery project, we obtain estimates of nucleotide diversity in windows spanning the human genome and show that the diversity to divergence ratio is reduced in regions of low recombination. Furthermore, we show that the elevated diversity in telomeric regions is mainly due to elevated mutation rates and not due to decreased levels of background selection. However, we find indications that telomeres as well as centromeres experience greater impact from natural selection than intrachromosomal regions. Finally, we identify a number of genomic regions with increased or reduced diversity compared with the local level of human-chimpanzee divergence and the local recombination rate.
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http://dx.doi.org/10.1101/gr.074187.107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493391PMC
July 2008

Genome sequence of the Brown Norway rat yields insights into mammalian evolution.

Nature 2004 Apr;428(6982):493-521

Human Genome Sequencing Center, Department of Molecular and Human Genetics, Baylor College of Medicine, MS BCM226, One Baylor Plaza, Houston, Texas 77030, USA. http://www.hgsc.bcm.tmc.edu

The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
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http://dx.doi.org/10.1038/nature02426DOI Listing
April 2004

Antiestrogen resistance in breast cancer and the role of estrogen receptor signaling.

Oncogene 2003 Oct;22(47):7316-39

Department of Oncology and Vincent T. Lombardi Cancer Center, Georgetown University School of Medicine, 3970 Reservoir Road NW, Washington, DC 20057, USA.

Antiestrogens include agents such as tamoxifen, toremifene, raloxifene, and fulvestrant. Currently, tamoxifen is the only drug approved for use in breast cancer chemoprevention, and it remains the treatment of choice for most women with hormone receptor positive, invasive breast carcinoma. While antiestrogens have been available since the early 1970s, we still do not fully understand their mechanisms of action and resistance. Essentially, two forms of antiestrogen resistance occur: de novo resistance and acquired resistance. Absence of estrogen receptor (ER) expression is the most common de novo resistance mechanism, whereas a complete loss of ER expression is not common in acquired resistance. Antiestrogen unresponsiveness appears to be the major acquired resistance phenotype, with a switch to an antiestrogen-stimulated growth being a minor phenotype. Since antiestrogens compete with estrogens for binding to ER, clinical response to antiestrogens may be affected by exogenous estrogenic exposures. Such exposures include estrogenic hormone replacement therapies and dietary and environmental exposures that directly or indirectly increase a tumor's estrogenic environment. Whether antiestrogen resistance can be conferred by a switch from predominantly ERalpha to ERbeta expression remains unanswered, but predicting response to antiestrogen therapy requires only measurement of ERalpha expression. The role of altered receptor coactivator or corepressor expression in antiestrogen resistance also is unclear, and understanding their roles may be confounded by their ubiquitous expression and functional redundancy. We have proposed a gene network approach to exploring the mechanistic aspects of antiestrogen resistance. Using transcriptome and proteome analyses, we have begun to identify candidate genes that comprise one component of a larger, putative gene network. These candidate genes include NFkappaB, interferon regulatory factor-1, nucleophosmin, and the X-box binding protein-1. The network also may involve signaling through ras and MAPK, implicating crosstalk with growth factors and cytokines. Ultimately, signaling affects the expression/function of the proliferation and/or apoptotic machineries.
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http://dx.doi.org/10.1038/sj.onc.1206937DOI Listing
October 2003

Human chromosome 7: DNA sequence and biology.

Science 2003 May 10;300(5620):767-72. Epub 2003 Apr 10.

Department of Genetics and Genomic Biology, The Hospital for Sick Children, Toronto, Ontario, Canada, M5G 1X8.

DNA sequence and annotation of the entire human chromosome 7, encompassing nearly 158 million nucleotides of DNA and 1917 gene structures, are presented. To generate a higher order description, additional structural features such as imprinted genes, fragile sites, and segmental duplications were integrated at the level of the DNA sequence with medical genetic data, including 440 chromosome rearrangement breakpoints associated with disease. This approach enabled the discovery of candidate genes for developmental diseases including autism.
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http://dx.doi.org/10.1126/science.1083423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882961PMC
May 2003

The genome sequence of the malaria mosquito Anopheles gambiae.

Science 2002 Oct;298(5591):129-49

Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA.

Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.
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http://dx.doi.org/10.1126/science.1076181DOI Listing
October 2002

Recent segmental duplications in the human genome.

Science 2002 Aug;297(5583):1003-7

Department of Genetics, Center for Computational Genomics, and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA.

Primate-specific segmental duplications are considered important in human disease and evolution. The inability to distinguish between allelic and duplication sequence overlap has hampered their characterization as well as assembly and annotation of our genome. We developed a method whereby each public sequence is analyzed at the clone level for overrepresentation within a whole-genome shotgun sequence. This test has the ability to detect duplications larger than 15 kilobases irrespective of copy number, location, or high sequence similarity. We mapped 169 large regions flanked by highly similar duplications. Twenty-four of these hot spots of genomic instability have been associated with genetic disease. Our analysis indicates a highly nonrandom chromosomal and genic distribution of recent segmental duplications, with a likely role in expanding protein diversity.
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http://dx.doi.org/10.1126/science.1072047DOI Listing
August 2002

Association of interferon regulatory factor-1, nucleophosmin, nuclear factor-kappaB, and cyclic AMP response element binding with acquired resistance to Faslodex (ICI 182,780).

Cancer Res 2002 Jun;62(12):3428-37

Vincent T. Lombardi Cancer Center and Department of Oncology, Georgetown University School of Medicine, Washington, DC 20007, USA.

To identify genes associated with survival from antiestrogens, both serial analysis of geneexpression and gene expression microarrays were used to explore the transcriptomes of antiestrogen-responsive (MCF7/LCC1) and -resistant variants(MCF7/LCC9) of the MCF-7 human breast cancer cell line. Structure of the gene microarray expression data was visualized at the top level using a novel algorithm that derives the first three principal components,fitted to the antiestrogen-resistant and -responsive gene expression data, from Fisher's information matrix. The differential regulation of several candidate genes was confirmed. Functional studies of the basal expression and endocrine regulation of transcriptional activation of implicated transcription factors were studied using promoter-reporter assays. The putative tumor suppressor interferon regulatory factor-1 is down-regulated in resistant cells, whereas its nucleolar phosphoprotein inhibitor nucleophosmin is up-regulated. Resistant cells also up-regulate the transcriptional activation of cyclic AMP response element (CRE) binding and nuclear factor kappaB (NFkappaB) while down-regulating epidermal growth factor receptor protein expression. Inhibition of NFkappaB activity by ICI 182,780 is lost in resistant cells, but CRE activity is not regulated by ICI 182,780 in either responsive or resistant cells. Parthenolide, a potent and specific inhibitor of NFkappaB, inhibits the anchorage-dependent proliferation of antiestrogen-resistant but not antiestrogen-responsive cells. This observation implies a greater reliance on their increased NFkappaB signaling for proliferation in cells that have survived prolonged exposure to ICI 182,780. These data from serial analysis of gene expression and gene microarray studies implicate changes in a novel signaling pathway, involving interferon regulatory factor-1, nucleophosmin, NFkappaB, and CRE binding in cell survival after antiestrogen exposure. Cells can up-regulate some estrogen-responsive genes while concurrently losing the ability of antiestrogens to regulate their expression. Signaling pathways that are not regulated by estrogens also can be up-regulated. Thus, some breast cancer cells may survive antiestrogen treatment by bypassing specific growth inhibitory signals induced by antagonist-occupied estrogen receptors.
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June 2002

A comparison of whole-genome shotgun-derived mouse chromosome 16 and the human genome.

Science 2002 May;296(5573):1661-71

Celera Genomics, 45 West Gude Drive, Rockville, MD 20850, USA.

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.
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http://dx.doi.org/10.1126/science.1069193DOI Listing
May 2002

Iterative normalization of cDNA microarray data.

IEEE Trans Inf Technol Biomed 2002 Mar;6(1):29-37

Department of Electrical Engineering and Computer Science, The Catholic University of America, Washington, DC 20064, USA.

This paper describes a new approach to normalizing microarray expression data. The novel feature is to unify the tasks of estimating normalization coefficients and identifying control gene set. Unification is realized by constructing a window function over the scatter plot defining the subset of constantly expressed genes and by affecting optimization using an iterative procedure. The structure of window function gates contributions to the control gene set used to estimate normalization coefficients. This window measures the consistency of the matched neighborhoods in the scatter plot and provides a means of rejecting control gene outliers. The recovery of normalizational regression and control gene selection are interleaved and are realized by applying coupled operations to the mean square error function. In this way, the two processes bootstrap one another. We evaluate the technique on real microarray data from breast cancer cell lines and complement the experiment with a data cluster visualization study.
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http://dx.doi.org/10.1109/4233.992159DOI Listing
March 2002