Next big thing

News

Nature 444, 130-131 (9 November 2006) | doi:10.1038/444130a; Published online 8 November 2006

It’s the junk that makes us human!

Erika Check

‘Non-coding’ DNA may organize brain cell connections.

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GGtools

This paper reviews the central concepts and implementation of data structures and methods for studying genetics of gene expression with the GGtools package of Bioconductor. Illustration with a HapMap+expression dataset is provided.

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Outlier sums for differential gene expression analysis

Tibshirani and Hastie

We propose a method for detecting genes that, in a disease group, exhibit unusually high gene expression in some but not all samples. This can be particularly useful in cancer studies, where mutations that can amplify or turn off gene expression often occur in only a minority of samples. In real and simulated examples, the new method often exhibits lower false discovery rates than simple t-statistic thresholding. We also compare our approach to the recent cancer profile outlier analysis proposal of Tomlins and others (2005).

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Relationships between p63 Binding, DNA Sequence, Transcription Activity, and Biological Function in Human Cells

From Church, GIngeras, and Struhl

Using tiled microarrays covering the entire human genome, we identify 5800 target sites for p63, a p53 homolog essential for stratified epithelial development. p63 targets are enriched for genes involved in cell adhesion, proliferation, death, and signaling pathways. The quality of the derived DNA sequence motif for p63 targets correlates with binding strength binding in vivo, but only a small minority of motifs in the genome is bound by p63. Conversely, many p63 targets have motif scores expected for random genomic regions. Thus, p63 binding in vivo is highly selective and often requires additional factors beyond the simple protein-DNA interaction. There is a significant, but complex, relationship between p63 target sites and p63-responsive genes, with ΔNp63 isoforms being linked to transcriptional activation. Many p63 binding regions are evolutionarily conserved and/or associated with sequence motifs for other transcription factors, suggesting that a substantial portion of p63 sites is biologically relevant.

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Affy vs. NimbleGen vs. PCR from Gerstein group

Assessing the performance of different high-density tiling microarray strategies for mapping transcribed regions of the human genome

Genomic tiling microarrays have become a popular tool for interrogating the transcriptional activity of large regions of the genome in an unbiased fashion. There are several key parameters associated with each tiling experiment (e.g., experimental protocols and genomic tiling density). Here, we assess the role of these parameters as they are manifest in different tiling-array platforms used for transcription mapping. First, we analyze how a number of published tiling-array experiments agree with established gene annotation on human chromosome 22. We observe that the transcription detected from high-density arrays correlates substantially better with annotation than that from other array types. Next, we analyze the transcription-mapping performance of the two main high-density oligonucleotide array platforms in the ENCODE regions of the human genome. We hybridize identical biological samples and develop several ways of scoring the arrays and segmenting the genome into transcribed and nontranscribed regions, with the aim of making the platforms most comparable to each other. Finally, we develop a platform comparison approach based on agreement with known annotation. Overall, we find that the performance improves with more data points per locus, coupled with statistical scoring approaches that properly take advantage of this, where this larger number of data points arises from higher genomic tiling density and the use of replicate arrays and mismatches. While we do find significant differences in the performance of the two high-density platforms, we also find that they complement each other to some extent. Finally, our experiments reveal a significant amount of novel transcription outside of known genes, and an appreciable sample of this was validated by independent experiments.

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Journals

PK: Cell, Nat Mol Sys Bio, Genome Biology,

SWK: PLoS Medicine, Nature Medicine, Genome Research, Bioinformatics, Biostatistics

HL: PLoS Comp Bio,

PJP: Nature Biotech, Nature Methods, J of Comp Biology

SP: PNAS, NAR, BMC Bioinformatics, BMC Genomics

Still to add: Nat Review journals, OMICS, EMBO Journal, Current Opinions in Genetics & Development, Trends series, Physiological Genomics

lab meeting schedule

Dec 5/6 Peter P./Peter K.

Dec 12/13 Hailey/Peter P.

Dec 19/20 Shouyong/Hailey

Dec 26/27 Happy holidays!

Jan 2/3 Happy holidays!

Jan 9/10 No meetings (Peter is away)

Jan 16/17 Steve/Shouyong

Seminars: Vince Pirrotta, Genetics seminar Dec 13, noon