Empowering statistical methods for cellular and molecular biologists.

We provide guidelines for using statistical methods to analyze the types of experiments reported in cellular and molecular biology journals such as Molecular Biology of the Cell. Our aim is to help experimentalists use these methods skillfully, avoid mistakes, and extract the maximum amount of information from their laboratory work. We focus on comparing the average values of control and experimental samples. A Supplemental Tutorial provides examples of how to analyze experimental data using R software

Understanding drivers of species distribution change: a trait-based approach

The impacts of anthropogenic environmental change on biodiversity are well documented, with threats such as habitat loss and climate change identified as causes of change in species distributions. The high degree of variation in responses of species to environmental change can be partly explained through comparative analyses of species traits. I carried out a phylogenetically informed trait-based analysis of plant range change in Britain, discovering that traits associated with competitive ability and habitat specialism both explained variation in range changes. Competitive, habitat generalists out-perform ed species specialised to nutrient-poor conditions; a result which can be attributed to the impact of agricultural intensification in Britain. A limitation of the comparative approach is that the models do not directly test the impact of environmental change on species distribution patterns, but instead infer potential impacts. I tested the potential of comparative analyses from a spatial context by conducting a spatial analysis of plant distribution change in Britain, examining the direct impact of environmental change on the spatial distribution of the trait characteristics of species that have gone locally extinct. I discovered a loss of species associated with nitrogen poor soils in regions that had an increase in arable land cover, a result that supports the results from the trait-based analysis of plant range change and demonstrates that comparative studies can accurately infer drivers of distribution change. I found that the cross-region transferability of trait-based models of range change to be related to land cover similarity, highlighting that the trait-based approach is dependent on a regional context. Additionally, I discovered that traits derived from distribution data were significant predictors of range shift across many taxonomic groups, out-performing traditional life history traits. This thesis highlights the potential of the data accumulated through the increased public participation in biological recording to address previously unanswerable ecological research questions.Open Acces

Methods for Joint Normalization and Comparison of Hi-C data

The development of chromatin conformation capture technology has opened new avenues of study into the 3D structure and function of the genome. Chromatin structure is known to influence gene regulation, and differences in structure are now emerging as a mechanism of regulation between, e.g., cell differentiation and disease vs. normal states. Hi-C sequencing technology now provides a way to study the 3D interactions of the chromatin over the whole genome. However, like all sequencing technologies, Hi-C suffers from several forms of bias stemming from both the technology and the DNA sequence itself. Several normalization methods have been developed for normalizing individual Hi-C datasets, but little work has been done on developing joint normalization methods for comparing two or more Hi-C datasets. To make full use of Hi-C data, joint normalization and statistical comparison techniques are needed to carry out experiments to identify regions where chromatin structure differs between conditions. We develop methods for the joint normalization and comparison of two Hi-C datasets, which we then extended to more complex experimental designs. Our normalization method is novel in that it makes use of the distance-dependent nature of chromatin interactions. Our modification of the Minus vs. Average (MA) plot to the Minus vs. Distance (MD) plot allows for a nonparametric data-driven normalization technique using loess smoothing. Additionally, we present a simple statistical method using Z-scores for detecting differentially interacting regions between two datasets. Our initial method was published as the Bioconductor R package HiCcompare [http://bioconductor.org/packages/HiCcompare/](http://bioconductor.org/packages/HiCcompare/). We then further extended our normalization and comparison method for use in complex Hi-C experiments with more than two datasets and optional covariates. We extended the normalization method to jointly normalize any number of Hi-C datasets by using a cyclic loess procedure on the MD plot. The cyclic loess normalization technique can remove between dataset biases efficiently and effectively even when several datasets are analyzed at one time. Our comparison method implements a generalized linear model-based approach for comparing complex Hi-C experiments, which may have more than two groups and additional covariates. The extended methods are also available as a Bioconductor R package [http://bioconductor.org/packages/multiHiCcompare/](http://bioconductor.org/packages/multiHiCcompare/). Finally, we demonstrate the use of HiCcompare and multiHiCcompare in several test cases on real data in addition to comparing them to other similar methods (https://doi.org/10.1002/cpbi.76)

Identification of binary cellular automata from spatiotemporal binary patterns using a fourier representation

The identification of binary cellular automata from spatio-temporal binary patterns is investigated in this paper. Instead of using the usual Boolean or multilinear polynomial representation, the Fourier transform representation of Boolean functions is employed in terms of a Fourier basis. In this way, the orthogonal forward regression least-squares algorithm can be applied directly to detect the significant terms and to estimate the associated parameters. Compared with conventional methods, the new approach is much more robust to noise. Examples are provided to illustrate the effectiveness of the proposed approach

Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms

BACKGROUND: Adenosine-5'-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established. We tested the potential of urinary ATP in the assessment of lower urinary tract symptoms, infection and inflammation, and validated sampling methods for clinical practice. METHODS: A prospective, blinded, cross-sectional observational study of adult patients presenting with lower urinary tract symptoms (LUTS) and asymptomatic controls, was conducted between October 2009 and October 2012. Urinary ATP was assayed by a luciferin-luciferase method, pyuria counted by microscopy of fresh unspun urine and symptoms assessed using validated questionnaires. The sample collection, storage and processing methods were also validated. RESULTS: 75 controls and 340 patients with LUTS were grouped as without pyuria (n = 100), pyuria 1-9 wbc ?l(-1) (n = 120) and pyuria ?10 wbc ?l(-1) (n = 120). Urinary ATP was higher in association with female gender, voiding symptoms, pyuria greater than 10 wbc ?l(-1) and negative MSU culture. ROC curve analysis showed no evidence of diagnostic test potential. The urinary ATP signal decayed with storage at 23°C but was prevented by immediate freezing at ??-20°C, without boric acid preservative and without the need to centrifuge urine prior to freezing. CONCLUSIONS: Urinary ATP may have a role as a research tool but is unconvincing as a surrogate, clinical diagnostic marker