Motivation and Results: Durbin et al. (2002), Huber et al. (2002) and Munson (2001) independently introduced a family of transformations (the generalized-log family) which stabilizes the variance of microarray data up to the first order. We introduce a method for estimating the transformation parameter in tandem with a linear model based on the procedure outlined in Box and Cox (1964). We also discuss means of finding transformations within the generalized-log family which are optimal under other criteria, such as minimum residual skewness and minimum mean-variance dependency. Availability: R and Matlab code and test data are available from the authors on request. Contact: bpdurbin@ucdavis.edu

Motivation: Authors of several recent papers have independently introduced a family of transformations (the generalized-log family), which stabilizes the variance of microarray data up to the first order. However, for data from two-color arrays, tests for differential expression may require that the variance of the difference of transformed observations be constant, rather than that of the transformed observations themselves. Results: We introduce a transformation within the generalized-log family which stabilizes, to the first order, the variance of the difference of transformed observations. We also introduce transformations from the ‘started-log’ and log-linear-hybrid families which provide good approximate variance stabilization of differences. Examples using control–control data show that any of these transformations may provide sufficient variance stabilization for practical applications, and all perform well compared to log ratios.

Lactase persistence (LP) is a trait in which lactose can be digested throughout adulthood, while lactase non-persistence (LNP) can cause lactose intolerance and influence dairy consumption. One single nucleotide polymorphism (SNP ID: rs4988235) is often used as a predictor for dairy intake, since it is responsible for LP in people in European descent, and can occur in other ethnic groups. The objective of this study was to determine whether rs4988235 genotypes and ethnicity influence reported dairy consumption in the United States (U.S.). A food frequency questionnaire (FFQ) and multiple Automated Self-Administered 24-h recalls (ASA24^®) were used to measure habitual and recent intake, respectively, of total dairy, cheese, cow’s milk, plant-based alternative milk, and yogurt in a multi-ethnic U.S. cohort genotyped for rs4988235. Within Caucasian subjects, LP individuals reported consuming more recent total dairy and habitual total cow’s milk intake. For subjects of all ethnicities, LP individuals consumed more cheese (FFQ p = 0.043, ASA24 p = 0.012) and recent total dairy (ASA24 p = 0.005). For both dietary assessments, Caucasians consumed more cheese than all non-Caucasians (FFQ p = 0.036, ASA24 p = 0.002) independent of genotype, as well as more recent intake of yogurt (ASA24 p = 0.042). LP subjects consumed more total cow’s milk than LNP, but only when accounting for whether subjects were Caucasian or not (FFQ p = 0.015). Fluid milk and alternative plant-based milk consumption were not associated with genotypes or ethnicity. Our results show that both LP genotype and ethnicity influence the intake of some dairy products in a multi-ethnic U.S. cohort, but the ability of rs4988235 genotypes to predict intake may depend on ethnic background, the specific dairy product, and whether intake is reported on a habitual or recent basis. Therefore, ethnicity and the dietary assessment method should also be considered when determining the suitability of rs4988235 as a proxy for dairy intake.

Early signs of canine transitional cell carcinoma (TCC) are frequently assumed to be caused by other lower urinary tract diseases (LUTD) such as urinary tract infections, resulting in late diagnosis of TCC which could be fatal. The development of a non-invasive clinical test for TCC could dramatically reduce mortality. To determine whether microRNAs (miRNAs) can be used as non-invasive diagnostic biomarkers, we assessed miRNA expression in blood and/or urine from dogs with clinically normal bladders (n = 28), LUTD (n = 25), and TCC (n = 17). Expression levels of 5 miRNA associated with TCC pathophysiology (miR-34a, let-7c, miR-16, miR-103b, and miR-106b) were assessed by quantitative real-time PCR. Statistical analyses using ranked ANOVA identified significant differences in miR-103b and miR-16 levels between urine samples from LUTD and TCC patients (miR-103b, p = 0.002; and miR-16, p = 0.016). No statistically significant differences in miRNA levels were observed between blood samples from LUTD versus TCC patients. Expression levels of miR-34a trended with miR-16, let-7c, and miR-103b levels in individual normal urine samples, however, this coordination was completely lost in TCC urine samples. In contrast, co-ordination of miR-34a, miR-16, let-7c, and miR-103b expression levels was maintained in blood samples from TCC patients. Our combined data indicate a potential role for miR-103b and miR-16 as diagnostic urine biomarkers for TCC, and that further investigation of miR-103b and miR-16 in the dysregulation of coordinated miRNA expression in bladder carcinogenesis is warranted.

Grapevine red blotch virus (GRBV) is a recently identified virus. Previous research indicates primarily a substantial impact on berry ripening in all varieties studied. The current study analyzed grapes’ primary and secondary metabolism across grapevine genotypes and seasons to reveal both conserved and variable impacts to GRBV infection. Vitis vinifera cv. Cabernet Sauvignon (CS) grapevines grafted on two different rootstocks (110R and 420A) were analyzed in 2016 and 2017. Metabolite profiling revealed a considerable impact on amino acid and malate acid levels, volatile aroma compounds derived from the lipoxygenase pathway, and anthocyanins synthesized in the phenylpropanoid pathway. Conserved transcriptional responses to GRBV showed induction of auxin-mediated pathways and photosynthesis with inhibition of transcription and translation processes mainly at harvest. There was an induction of plant-pathogen interactions at pre-veraison, for all genotypes and seasons, except for CS 110R in 2017. Lastly, differential co-expression analysis revealed a transcriptional shift from metabolic synthesis and energy metabolism to transcription and translation processes associated with a virus-induced gene silencing transcript. This plant-derived defense response transcript was only significantly upregulated at veraison for all genotypes and seasons, suggesting a phenological association with disease expression and plant immune responses.