Independent filtering increases detection power for high-throughput experiments

Bourgon, Richard; Gentleman, Robert; Huber, Wolfgang

doi:10.1073/pnas.0914005107

Cited by 645 publications

(653 citation statements)

References 24 publications

(23 reference statements)

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“…Data were pre-processed by robust spline normalization and variance stabilizing transformation using the Bioconductor lumi package 11,12 . The pre-processed data were filtered to include only probes with detection threshold p values of < 0.05 in 100% of biopsies in at least one of the four study arms, or in 100% of vaginal epithelial cell cultures, and to remove probes that had a low standard deviation (≤ 0.5) across all arrays, using the Bioconductor genefilter package 13 . Finally, probes without an Entrez ID were removed, leaving 1,928 probes in the rectal biopsies, and 6,699 probes in the vaginal epithelial cell cultures, for further statistical analysis.…”

Section: Quality Control and Processing Of Microarray And Mass Spectrmentioning

confidence: 99%

Mucosal effects of tenofovir 1% gel

Hladik

Burgener

Ballweber

et al. 2014

Preprint

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BACKGROUND Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against sexual HIV transmission. Because this is a new prevention strategy targeting large numbers of healthy people, we broadly assessed its effects on the mucosa. METHODS AND FINDINGS In MTN-007, a phase 1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies taken at baseline, after one application or after seven daily applications (15 subjects/arm). Experiments were repeated using primary vaginal epithelial cells from four healthy women. After seven days of administration, tenofovir 1% gel had broad-ranging biological effects on the rectal mucosa, which were much more pronounced than—but different from—those caused by the detergent nonoxynol-9. Tenofovir profoundly suppressed anti-inflammatory mediators such as interleukin 10; increased T cell densities; caused mitochondrial dysfunction, possibly by blocking PNPT1 expression; and altered regulatory pathways of cell differentiation and survival. Except for leukocyte-derived factors, all these effects were replicated in primary vaginal epithelial cells, which also proliferated significantly faster in tenofovir’s presence. CONCLUSIONS Tenofovir’s suppression of anti-inflammatory activity could diminish its prophylactic efficacy over time. The breadth of mucosal changes, including mitochondrial dysfunction and epithelial proliferation, raises questions about its safety for long-term topical use. These findings suggest that a systems biology evaluation of mucosal effects may be beneficial before advancing to large-scale efficacy trials with topical HIV prevention agents that achieve high, long-lasting local drug concentrations.

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Section: Quality Control and Processing Of Microarray And Mass Spectrmentioning

confidence: 99%

Mucosal effects of tenofovir 1% gel

Hladik

Burgener

Ballweber

et al. 2014

Preprint

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“…Previously, an independent filter based on the OTUs with an abundance of ≤2 counts and present in <3 biofilm samples (5%) was excluded from the statistical analysis [34]. …”

Section: Methodsmentioning

confidence: 99%

In situ substrate-formed biofilms using IDODS mimic supragingival tooth-formed biofilms

Tomás

Prada-López

Quintas

et al. 2018

Journal of Oral Microbiology

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This study aimed to compare the bacterial viability and diversity of a substrate-formed biofilm (SF-biofilm) in situ to a supragingival tooth-formed biofilm (TF-biofilm) in the same group of individuals. The impact of the device/disc position and toothbrushing during the formation of SF-biofilm was also assessed. Two tests were run. In test 1, 15 volunteers wore two hemi-splints carrying six discs of human enamel, glass, and hydroxyapatite for 2 days, and were instructed to not perform any oral hygiene measure. Biofilm samples were collected from the substrates and the contralateral tooth and were analysed using CLSM. In five volunteers, half of the biofilm present on the discs and their contralateral teeth were scraped and analysed using 16S pyrosequencing. In test 2, the microscopic analysis was repeated only on the SF-biofilm samples, and the volunteers were allowed to brush their teeth. Multivariate analyses revealed that the donors had a significant effect on the composition of the biofilm, confirming its subject-dependent character. The bacterial composition of the SF-biofilm was similar to the TF-biofilm, with significant differential abundance detected in very few taxa of low abundance. The toothbrushing during the formation of SF-biofilm was the only factor that conditioned the thickness or bacterial viability.

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“…A two step filtering approach was used instead. While two stage filtering approaches have been found to improve detection power over the familywise error rate or false discovery rate approaches, it has been suggested that this approach can lead to type I errors [3].…”

Section: Discussion and Significancementioning

confidence: 99%

Can miRNA profiling allow us to determine which patients with esophageal cancer will respond to chemoradiotherapy?

Mayne

Hussey

Watson

2013

Expert Review of Anticancer Therapy

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Most patients undergoing surgery for esophageal cancer are treated before surgery with chemotherapy and radiotherapy. However, some tumors respond poorly to these treatments. Ko and colleagues profiled microRNA levels in esophageal cancers from patients who did vs. did not respond to chemoradiotherapy. A large number of microRNAs were differentially expressed between responders vs. non-responders, and patients with either decreased miR-135b or increased miR-145 expression in cancer tissue had improved disease free survival. Although this study has several limitations, including a mixed cohort of patients with adenocarcinoma and squamous cell carcinoma, and the absence of a validation set of patients, the results do suggest that a microRNA profiling approach may be able to circumvent one of the primary challenges for biomarker development, molecular heterogeneity. Word count = 124Title: concise, not more than 120 characters.Can microRNA profiling allow us to determine which patients with esophageal cancer will respond to chemoradiotherapy?Keywords: approximately 5-10 keywords for the review.

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Independent filtering increases detection power for high-throughput experiments

Cited by 645 publications

References 24 publications

Mucosal effects of tenofovir 1% gel

Mucosal effects of tenofovir 1% gel

In situ substrate-formed biofilms using IDODS mimic supragingival tooth-formed biofilms

Can miRNA profiling allow us to determine which patients with esophageal cancer will respond to chemoradiotherapy?

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