SubcloneSeeker: a computational framework for reconstructing tumor clone structure for cancer variant interpretation and prioritization

Many tumors are composed of genetically divergent cell subpopulations. We report SubcloneSeeker, a package capable of exhaustive identification of subclone structures and evolutionary histories with bulk somatic variant allele frequency measurements from tumor biopsies. We present a statistical framework to elucidate whether specific sets of mutations are present within the same subclones, and the order in which they occur. We demonstrate how subclone reconstruction provides crucial information about tumorigenesis and relapse mechanisms; guides functional study by variant prioritization, and has the potential as a rational basis for informed therapeutic strategies for the patient. SubcloneSeeker is available at: https://github.com/yiq/SubcloneSeeker.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0443-x) contains supplementary material, which is available to authorized users.     

HeatMapper: powerful combined visualization of gene expression profile correlations, genotypes, phenotypes and sample characteristics

Background  

Accurate interpretation of data obtained by unsupervised analysis of large scale expression profiling studies is currently frequently performed by visually combining sample-gene heatmaps and sample characteristics. This method is not optimal for comparing individual samples or groups of samples. Here, we describe an approach to visually integrate the results of unsupervised and supervised cluster analysis using a correlation plot and additional sample metadata.     

A mathematical model for pH patterns in the rhizospheres of growth zones

In the classical model by Nye (1981), the main process for the change in pH across the rhizosphere is assumed to be diffusion. The classical model focuses on the non-growing part of the root and assumes that the distribution of ion fluxes along the root is spatially uniform. We consider the rhizosphere of the growth zone and take into account the root growth rate and spatially varying flux along the root surface. We present both analytical (dimensional analysis) and experimental (computational) evidence of the importance of taking into account the root growth rate. We describe a conceptual and mathematical model to analyse the pH field around the root tip over time. The model is used with published data to show that, for typical growth rates in sandy soil, the pH field becomes steady (independent of time) after 6 h. Dimensional analysis reveals that a version of the Péclet number, related to the quotient of root elongation rate and proton diffusivity, can be used to predict the extent of the rhizosphere and the time required for it to become steady. For Péclet numbers much greater than 1 (soils), the root influences soil pH for distances on the millimetre scale. In contrast, for Péclet numbers much less than one (agar, aqueous solution), the root influences substrate pH for radial distances on the scale of centimetres. We also present some evidence that agar-contact techniques to measure the soil pH may not be appropriate for measuring the millimetre-scale gradients in soil pH.     

Mother-infant relationships in bonnet macaques: Sources of variation in proximity

Family composition is an important predictor of variation in proximity among captive bonnet macaque (Macaca radiata) mothers and their infants. Infants that have several immature sisters in the group are initially more independent that infants with fewer sisters, but as they reach 6 months of age infants with several sisters become less independent than their peers. The effects of the presence of juvenile females on the relative independence of their infant siblings seem to be related to the fact that the members of families with several immature females are the targets of more aggression than are the members of other families.     

A practical guide to the study of social relationships

Behavioral ecologists have devoted considerable effort to identifying the sources of variation in individual reproductive success. 1 - 5 Much of this work has focused on the characteristics of individuals, such as their sex and rank. However, many animals live in stable social groups and the fitness of individuals depends at least in part on the outcome of their interactions with other group members. For example, in many primate species, high dominance rank enhances access to resources and reproductive success. 4 , 5 The ability to acquire and maintain high rank often depends on the availability and effectiveness of coalitionary support. 6 Allies may be cultivated and coalitions may be reinforced by affiliative interactions such as grooming, food sharing, and tolerance. 7 , 8 These findings suggest that if we want to understand the selective pressures that shape the social behavior of primates, it will be profitable to broaden our focus from the characteristics of individuals to the properties of the relationships that they form with others. The goal of this paper is to discuss a set of methods that can be used to quantify the properties of social relationships.