ACHIKO-M Database for high myopia analysis and its evaluation

Myopia is the leading public health concern with high prevalence in developed countries. In this paper, we present the ACHIKO-M fundus image database with both myopic and emmetropic cases for high myopia study. The database contains 705 myopic subjects and 151 normal subjects with both left eye and right eye images for each subject. In addition, various clinical data is also available, allowing correlation study of different risk factors. We evaluated two state-of-the-art automated myopia detection algorithms on this database to show how it can be used. Both methods achieve more than 90% accuracy for myopia diagnosis. We will also discuss how ACHIKO-M can be a good database for both scientific and clinical research of myopia

Tumor Transcriptome Sequencing Reveals Allelic Expression Imbalances Associated with Copy Number Alterations

Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas. Additionally, to better understand the genomic determinants of the gene expression changes observed, we have sequenced the tumor and normal genomes of one of these patients. We demonstrate here that our RNA-Seq method accurately measures allelic imbalance and that measurement on the genome-wide scale yields novel insights into cancer etiology. As expected, the set of genes differentially expressed in the tumors is enriched for cell adhesion and differentiation functions, but, unexpectedly, the set of allelically imbalanced genes is also enriched for these same cancer-related functions. By comparing the transcriptomic perturbations observed in one patient to his underlying normal and tumor genomes, we find that allelic imbalance in the tumor is associated with copy number mutations and that copy number mutations are, in turn, strongly associated with changes in transcript abundance. These results support a model in which allele-specific deletions and duplications drive allele-specific changes in gene expression in the developing tumor

Abstract 2117: Detection of rare mutations in patient samples by comparative allele-specific TaqMan® assay-based PCR (CastPCR)

Abstract Circulating tumor cells and circulating tumor DNA in the blood of cancer patient may carry cancer-associated mutations. Detection of these mutations directly from the blood of cancer patient is the key to early cancer diagnosis. Here we report a new comparative allele-specific TaqMan® assay-based PCR (CastPCR) method for rare mutation detection. CastPCR combines allele-specific TaqMan® assay with allele-specific MGB-modified blockers to suppress amplification of the wild type allele. We have demonstrated that CastPCR has TaqMan® assay-like sensitivity, linearity and dynamic range; can detect single mutant molecule in the presence of 1 million wild-type molecules; and can detect rare cancer-associated mutations in cancer patient samples. CastPCR will have broad applications in cancer research and in cancer diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2117.</jats:p

A systems biology approach to studying the molecular mechanisms of osteoblastic differentiation under cytokine combination treatment

AbstractRecent studies revealed that sequential release of bone morphogenetic protein 2 and insulin-like growth factor 1 plays an important role in osteogenic process, suggesting that cytokines bone morphogenetic protein 2 and insulin-like growth factor 1 function in a time-dependent manner. However, the specific molecular mechanisms underlying these observations remained elusive, impeding the elaborate manipulation of cytokine sequential delivery in tissue repair. The aim of this study was to identify the key relevant pathways and processes regulating bone morphogenetic protein 2/insulin-like growth factor 1-mediated osteoblastic differentiation. Based on the microarray and proteomics data, and differentiation/growth status of mouse bone marrow stromal cells, we constructed a multiscale systems model to simulate the bone marrow stromal cells lineage commitment and bone morphogenetic protein 2 and insulin-like growth factor 1-regulated signaling dynamics. The accuracy of our model was validated using a set of independent experimental data. Our study reveals that, treatment of bone marrow stromal cells with bone morphogenetic protein 2 prior to insulin-like growth factor 1 led to the activation of transcription factor Runx2 through TAK1-p38 MAPK and SMAD1/5 signaling pathways and initiated the lineage commitment of bone marrow stromal cells. Delivery of insulin-like growth factor 1 four days after bone morphogenetic protein 2 treatment optimally activated transcription factors osterix and β-catenin through ERK and AKT pathways, which are critical to preosteoblast maturity. Our systems biology approach is expected to provide technical and scientific support in optimizing therapeutic scheme to improve osteogenesis/bone regeneration and other essential biological processes.</jats:p