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slepr a sample-level enrichment-based pathway ranking method — seeking biological themes through pathway-level consistencyslepr一sample-level enrichment-based路径排序法u2014u2014通过pathway-level寻求生物主题一致性.pdfVIP

slepr a sample-level enrichment-based pathway ranking method — seeking biological themes through pathway-level consistencyslepr一sample-level enrichment-based路径排序法u2014u2014通过pathway-level寻求生物主题一致性.pdf

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slepr a sample-level enrichment-based pathway ranking method — seeking biological themes through pathway-level consistencyslepr一sample-level enrichment-based路径排序法u2014u2014通过pathway-level寻求生物主题一致性

SLEPR: A Sample-Level Enrichment-Based Pathway Ranking Method — Seeking Biological Themes through Pathway-Level Consistency Ming Yi, Robert M. Stephens* Advanced Biomedical Computing Center, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland, United States of America Abstract Analysis of microarray and other high throughput data often involves identification of genes consistently up or down- regulated across samples as the first step in extraction of biological meaning. This gene-level paradigm can be limited as a result of valid sample fluctuations and biological complexities. In this report, we describe a novel method, SLEPR, which eliminates this limitation by relying on pathway-level consistencies. Our method first selects the sample-level differentiated genes from each individual sample, capturing genes missed by other analysis methods, ascertains the enrichment levels of associated pathways from each of those lists, and then ranks annotated pathways based on the consistency of enrichment levels of individual samples from both sample classes. As a proof of concept, we have used this method to analyze three public microarray datasets with a direct comparison with the GSEA method, one of the most popular pathway-level analysis methods in the field. We found that our method was able to reproduce the earlier observations with significant improvements in depth of coverage for validated or expected biological themes, but also produced additional insights that make biological sense. This new method extends existing analyses approaches and facilitates integration of different types of HTP data. Citation: Yi M, Stephens RM (2008) SLEPR: A Sample-Level Enrichment-Based Pathway Ranking Method — Seeking Biological Themes through Pathway-Level Consistency. PLoS ONE 3(9): e3288. doi:10.1371/journa

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