From single-SNP to wide-locus: genome-wide association studies identifying functionally related genes and intragenic regions in small sample studies.

BACKGROUND: Genome-wide association studies (GWAS) have had limited success when applied to complex diseases. Analyzing SNPs individually requires several large studies to integrate the often divergent results. In the presence of epistasis, multivariate approaches based on the linear model (including stepwise logistic regression) often have low sensitivity and generate an abundance of artifacts. METHODS: Recent advances in distributed and parallel processing spurred methodological advances in nonparametric statistics. U-statistics for structured multivariate data (µStat) are not confounded by unrealistic assumptions (e.g., linearity, independence). RESULTS: By incorporating knowledge about relationships between SNPs, µGWAS (GWAS based on µStat) can identify clusters of genes around biologically relevant pathways and pinpoint functionally relevant regions within these genes. CONCLUSION: With this computational biostatistics approach increasing power and guarding against artifacts, personalized medicine and comparative effectiveness will advance while subgroup analyses of Phase III trials can now suggest risk factors for adverse events and novel directions for drug development.

Microbial populations associated with fixed- and floating-bed reactors during a two-stage anaerobic process

Microbial populations associated with methanogenic fixed- or floating-bed bioreactors used for anaerobic digestion of lignocellulosic waste were investigated. Fluorescent in situ hybridization (FISH) was used to characterize microorganisms in samples obtained from different heights in the reactors, which were operated in a semi-continuous manner (feeding and mixing once every 2 days). The FISH results showed that Methanosaeta concilii cells were most numerous at the bottom of both reactors. M. concilii cells were more abundant in the fixed-bed reactor (FXBR), which performed better than the floating-bed reactor (FLBR). Species of the Methanosarcina genera (mainly M. barkeri and M. mazei) were also observed in the FLBR but rarely in the FXBR. Methane production in each of the reactors ranged from 0.29 to 0.33 m3 CH(4)/kg COD(rem) (chemical oxygen demand removed). The removal of volatile fatty acids (VFA; 70-75 h) in the FXBR was more efficient than in the FLBR (AU)

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Microbial populations associated with fixed- and floating-bed reactors during a two-stage anaerobic process.

Microbial populations associated with methanogenic fixed- or floating-bed bioreactors used for anaerobic digestion of lignocellulosic waste were investigated. Fluorescent in situ hybridization (FISH) was used to characterize microorganisms in samples obtained from different heights in the reactors, which were operated in a semi-continuous manner (feeding and mixing once every 2 days). The FISH results showed that Methanosaeta concilii cells were most numerous at the bottom of both reactors. M. concilii cells were more abundant in the fixed-bed reactor (FXBR), which performed better than the floating-bed reactor (FLBR). Species of the Methanosarcina genera (mainly M. barkeri and M. mazei) were also observed in the FLBR but rarely in the FXBR. Methane production in each of the reactors ranged from 0.29 to 0.33 m3 CH(4)/kg COD(rem) (chemical oxygen demand removed). The removal of volatile fatty acids (VFA; 70-75 h) in the FXBR was more efficient than in the FLBR.