Alternative splicing of pre-mRNA generates protein diversity and has been linked to cancer progression and drug response. Exon microarray technology enables genome-wide quantication of expression levels for the majority of exons and facilitates the discovery of alternative splicing events. Analysis of exon array data is more challenging than gene expression data and there is a need for reliable quantication of exons and alternative spliced variants. We introduce a novel, computationally efficient methodology, MEAP, for exon array data preprocessing, analysis and visualization. We compared MEAP with other preprocessing methods, and validation of the results show that MEAP produces reliable quantication of exons and alternative spliced variants. Analysis of data from head and neck squamous cell carcinoma (HNSCC) cell lines revealed several variants associated with 11q13 amplication, which is a predictive marker of metastasis and decreased survival in HNSCC patients. Together these results demonstrate the utility of MEAP in suggesting novel experimentally testable predictions. Thus, in addition to novel methodology to process large-scale exon array data sets, our results provide several HNSCC candidate genes for further studies.
Comprehensive exon array data processing method for quantitative analysis of alternative spliced variants.
Cell line
View SamplesRNA-Seq experiment was done to compare cngc16 (a heat-sensitive mutant harboring a knockout of cyclic nucleotide-gated channel 16) and wild type pollen for differences in their response to a temperature stress condition. Transcriptomes were analyzed from mature pollen grains harvested at midday from plants grown under normal (control) conditions or a heat stress regime. For the stress condition, plants were grown under a diurnal cycle of hot and cold temperatures and pollen were harvested at the end of a HS period that peaked at 40 degrees Celsius.
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Specimen part, Treatment
View SamplesExosomes are 40~120 nm diameter vesicles of endocytic origin released by most cells and important in mediating cell-cell communication. As mRNA and noncoding RNA are two main functional RNA molecules in post transcription level and involves in many bio-activities including cancer progression and metastasis, it is important to understand the coding and noncoding genes contained within exosomes released by tumour cells. This study focused on the protein coding and noncoding genes enriched in two subtypes of exosomes (A33-enriched exosomes, A33-Exos and EpCAM-enriched exosomes, EpCAM-Exos) released by human colon cancer LIM1863 cell line. With high throughput sequencing technology and bioinformatics analyses, we demonstrate 350 protein coding genes (PCGs) and 222 noncoding genes (NCGs) are commonly enriched; 56 PCGs and 202 NCGs were specifically enriched in A33-Exos and 276 PCGs and 253 NCGs were enriched unique to EpCAM-Exos. A salient finding was the significant enrichment of TPT1, ribosomal protein genes and GAS5, a tumour noncoding gene, in exosomes. We further demonstrate differentially seven expressed genes (SCARB1, SCD, TPT1, EETF1G, BCL7C, RPS3, and RAB13) by qRT-PCR. Importantly, we correlated these findings with several matched tissue-derived tumour-normal samples showed TPT1 and ribosomal protein genes were up regulated in human tumour samples. Our findings provide a new insight of functional RNA molecules in exosomes and new select non-invasive biomarker candidates for colon cancer diagnosis and prognosis.
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No sample metadata fields
View SamplesTranscriptional response to plant extract
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Sex, Specimen part, Cell line, Treatment
View SamplesPediatric acute lymphoblastic leukemia (ALL) contains cytogenetically distinct subtypes that respond differently to cytotoxic drugs. Subtype classification can be also achieved through gene expression profiling. However, how to apply such classifiers to a single patient and correctly diagnose the disease subtype in an independent patient group has not been addressed. Furthermore, the underlying regulatory mechanisms responsible for the subtype-specific gene expression patterns are still largely unknown. Here, by combining three published microarray datasets (PMIDs: 12086872, 12730115, 17002788) on 535 Caucasian samples and generating a new dataset on 100 Chinese children ALL samples, we were able to 1) identify a 62-gene classifier with 97.6% accuracy from the Caucasian samples and validated it on the completely independent set of 100 Chinese samples, 2) to uncover potential regulatory networks of ALL subtypes. The classifier we identified was so far the only one that could be applied directly to a single sample and sustained validation in a large independent patient group. Our results also suggest that the etiology of ALL is largely the same among different ethnic groups, and that the transcription factor hubs in the predicted regulatory network might play important roles in regulating gene expression and development of ALL.
Gene expression-based classification and regulatory networks of pediatric acute lymphoblastic leukemia.
Specimen part, Disease, Race
View SamplesEthylene plays major roles in adaptive growth of rice plants in water-saturated soil; however, ethylene signaling in rice is largely unclear. Here, we report identification and characterization of ethylene-response mutants based on distinct ethylene-response phenotypes of dark-grown rice seedlings.
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Specimen part, Treatment
View SamplesRecent studies have demonstrated that human astrocytes and fibroblasts can be directly converted into functional neurons by small molecules. However, the reported reprogramming efficiency of human fibroblasts is extremely low, resulting in limited clinical application for the treatment of neurological disorders. Here, we report that human fibroblasts can be efficiently and directly reprogrammed into functional neuron-like cells (with a yield up to 82% TUJ1-positive neuron-like cells) by serially exposing cells to a combination of small molecules. These chemically induced neurons (iNs) displayed typical neuronal morphologies and showed neuronal transcriptional networks resembling human primary embryonic brain neurons. The iNs also exhibited mature firing patterns and formed functional synapse when cultured on mouse astrocytes. Importantly, the iNs can survive, mature and integrate into local circuits after transplantation into the postnatal mouse brains. Our study provides a rapid and efficient transgene-free approach for chemically generating neuron-like cells from human fibroblasts. Further, our approach offers strategies for disease modeling and drug discovery in central nervous system disorders.
Rapid and Efficient Conversion of Human Fibroblasts into Functional Neurons by Small Molecules.
Sex, Specimen part
View SamplesReceptor-like kinases (RLKs) play important roles in plant development and defense responses; however, their functions in other processes remain unclear. Here, we report that OsSIK2, an S-domain RLK from rice, is involved in abiotic stress and senescence process, integrating stress signals into developmental program for adaptive growth.
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Specimen part
View SamplesEthylene plays major roles in adaptive growth of rice plants in water-saturated soil; however, ethylene signaling in rice is largely unclear. Here, we report identification and characterization of ethylene-response mutants based on distinct ethylene-response phenotypes of dark-grown rice seedlings.
No associated publication
Specimen part, Treatment
View SamplesHistone methylation is a complex posttranslational modification regulating transcription and chromatin dynamics, and plays important roles in development and disease processes. Recent studies indicate that histone lysine methylation is a reversible modification and several JmjC-domain-containing proteins have been identified as histone lysine demethylases. Here we show that KIAA1718, a JmjC-domain-containing protein, is a histone demethylase. KIAA1718 demethylated dimethylation of H3 lysine 9 and 27 (H3K9me2 and H3K27me2), two important epigenetic marks associated with embryonic development6-10. In mouse embryonic stem cells (ESCs), KIAA1718 expression increased at the early phase of neural differentiation. RNA interference inhibition of KIAA1718 blocked neural differentiation and the effect was rescued by wild-type human gene, but not by a catalytically inactive mutant. In chick embryos, KIAA1718 is exclusively expressed in the epiblast cells of the primitive streak, an organizer contributing to neural induction. Knockdown of KIAA1718 resulted in defects in neural formation, while its overexpression led to neural expansion. The pro-neural effect is mediated through transcriptional activation of FGF4, a growth factor implicated in neural induction. Thus, our study identifies a dual specific histone demethylase as a novel epigenetic factor integrated with growth factor signaling, which has important roles in the early neural development.
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Specimen part, Cell line
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