Abstract 1991: Integrated analysis of copy number alteration and RNA expression profile in pediatric diffuse intrinsic pontine glioma
Bibliographic record
Abstract
Abstract DIPG is one of the most devastating of pediatric malignancies and one for which no effective therapy exists. A major contributor to the failure of therapeutic trials is the assumption that biologic properties of childhood brainstem tumors are identical to adult high-grade gliomas. A better understanding of the biology of DIPG itself is needed in order to develop agents targeted more specifically to these children's disease. Here we address this lack of knowledge by performing the first high-resolution, DNA- and RNA-microarray analysis of pediatric DIPG. Nine DIPGs were prospectively collected at post-mortem following consent for research purposes. Four pre-treatment surgical samples were also retrieved from our pathology archives. All samples were hybridized to Affymetrix SNP-arrays (250k or 6.0). Nine samples were also hybridized to the HumanRef-8 v3.0 (DASL) or HumanWG-6 v3.0 expression beadchip from Illumina. Data were analyzed using the Copy Number Analysis Tool (Affymetrix) and Partek Genomics Suite using HMM and segmentation algorithm for copy number and clustering algorithm for gene expression. DASL and Whole genome beadchip from Illumina have 18,404 probes in common. Those common probes were selected in the two data sets and the gene intensities related to those probes were pulled out for each sample separately. The differentially expressed genes were then identified using one-way ANOVA. For each sample, a gene list was created containing genes having a fold change between 2 and −2. The intersection of the seven gene lists was found using a Venn diagram. In total 234 genes were found that are differentially expressed in all seven samples. The gene expression and gene copy number data were then integrated. In total 5 genes show correlation between copy number and gene expression in all seven samples. Among the 234 differentially expressed genes, Ingenuity pathway analysis identified 63 genes associated with different aspect of cancer including proliferation, metastasis, polyploidization, neoplasia, adhesion, migration, survival, acidification, attachment, cell cycle progression, differentiation, growth and invasion. Our data provides the first, comprehensive, genomic analysis of pediatric DIPG. A thorough understanding of the genetic abnormalities in DIPG is a crucial first step in the development of targeted therapies for this devastating group of tumors. This is of particular importance for DIPG given the lack of efficacy of current treatment regimens and the dismal prognosis for these patients. 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 1991.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".