Non-Restarting CUSUM charts and Control of the False Discovery Rate

Cumulative sum (CUSUM) charts are typically used to detect changes in a stream of observations e.g. shifts in the mean. Usually, after signalling, the chart is restarted by setting it to some value below the signalling threshold. We propose a non-restarting CUSUM chart which is able to detect periods during which the stream is out of control. Further, we advocate an upper boundary to prevent the CUSUM chart rising too high, which helps detecting a change back into control. We present a novel algorithm to control the false discovery rate (FDR) pointwise in time when considering CUSUM charts based on multiple streams of data. We prove that the FDR is controlled under two definitions of a false discovery simultaneously. Simulations reveal the difference in FDR control when using these two definitions and other desirable definitions of a false discovery.Comment: 10 pages, 2 figure

Gene Expression During the First 28 Days of Axolotl Limb Regeneration I: Experimental Design and Global Analysis of Gene Expression

While it is appreciated that global gene expression analyses can provide novel insights about complex biological processes, experiments are generally insufficiently powered to achieve this goal. Here we report the results of a robust microarray experiment of axolotl forelimb regeneration. At each of 20 post-amputation time points, we estimated gene expression for 10 replicate RNA samples that were isolated from 1 mm of heterogeneous tissue collected from the distal limb tip. We show that the limb transcription program diverges progressively with time from the non-injured state, and divergence among time adjacent samples is mostly gradual. However, punctuated episodes of transcription were identified for five intervals of time, with four of these coinciding with well-described stages of limb regeneration—amputation, early bud, late bud, and pallet. The results suggest that regeneration is highly temporally structured and regulated by mechanisms that function within narrow windows of time to coordinate transcription within and across cell types of the regenerating limb. Our results provide an integrative framework for hypothesis generation using this complex and highly informative data set

Independent Domestication of Two Old World Cotton Species

Domesticated cotton species provide raw material for the majority of the world\u27s textile industry. Two independent domestication events have been identified in allopolyploid cotton, one in Upland cotton ( Gossypium hirsutum L.) and the other to Egyptian cotton ( Gossypium barbadense L.). However, two diploid cotton species, Gossypium arboreum L. and Gossypium herbaceum L., have been cultivated for several millennia, but their status as independent domesticates has long been in question. Using genome resequencing data, we estimated the global abundance of various repetitive DNAs. We demonstrate that, despite negligible divergence in genome size, the two domesticated diploid cotton species contain different, but compensatory, repeat content and have thus experienced cryptic alterations in repeat abundance despite equivalence in genome size. Evidence of independent origin is bolstered by estimates of divergence times based on molecular evolutionary analysis of f7,000 orthologous genes, for which synonymous substitution rates suggest that G. arboreum and G. herbaceum last shared a common ancestor approximately 0.4–2.5 Ma. These data are incompatible with a shared domestication history during the emergence of agriculture and lead to the conclusion that G. arboreum and G. herbaceum were each domesticated independently

A risk-adjusted CUSUM in continuous time based on the Cox model

There was a mistake in the contact information of the second author in the above paper (DOI: 10.1002/sim.3216 ). The correct affiliation is shown above. We apologise for the error and any inconvenience caused.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60222/1/3296_ftp.pd

Disturbed flow in an aquatic environment may create a sensory refuge for aggregated prey

Predators use olfactory cues moved within water and air to locate prey. Because prey aggregations may produce more cue and be easier to detect, predation could limit aggregation size. However, disturbance in the flow may diminish the reliability of odour as a prey cue, impeding predator foraging success and efficiency. We explore how different cue concentrations (as a proxy for prey group size) affect risk to prey by fish predators in disturbed (more turbulent or mixed) and non-disturbed (less mixed) flowing water. We find that increasing odour cue concentration increases predation risk and disturbing the flow reduces predation risk. At high cue concentration fish were able to locate the cue source in both disturbed and non-disturbed flow, but at medium concentrations, predators only located the cue source more often than expected by chance in non-disturbed flow. This suggests that objects disturbing flow provide a sensory refuge allowing prey to form larger groups, but that group sizes may be limited by level of disturbance to the flow

Evaluating Statistical Methods Using Plasmode Data Sets in the Age of Massive Public Databases: An Illustration Using False Discovery Rates

Plasmode is a term coined several years ago to describe data sets that are derived from real data but for which some truth is known. Omic techniques, most especially microarray and genomewide association studies, have catalyzed a new zeitgeist of data sharing that is making data and data sets publicly available on an unprecedented scale. Coupling such data resources with a science of plasmode use would allow statistical methodologists to vet proposed techniques empirically (as opposed to only theoretically) and with data that are by definition realistic and representative. We illustrate the technique of empirical statistics by consideration of a common task when analyzing high dimensional data: the simultaneous testing of hundreds or thousands of hypotheses to determine which, if any, show statistical significance warranting follow-on research. The now-common practice of multiple testing in high dimensional experiment (HDE) settings has generated new methods for detecting statistically significant results. Although such methods have heretofore been subject to comparative performance analysis using simulated data, simulating data that realistically reflect data from an actual HDE remains a challenge. We describe a simulation procedure using actual data from an HDE where some truth regarding parameters of interest is known. We use the procedure to compare estimates for the proportion of true null hypotheses, the false discovery rate (FDR), and a local version of FDR obtained from 15 different statistical methods

Population gene introgression and high genome plasticity for the zoonotic pathogen Streptococcus agalactiae

The influence that bacterial adaptation (or niche partitioning) within species has on gene spillover and transmission among bacteria populations occupying different niches is not well understood. Streptococcus agalactiae is an important bacterial pathogen that has a taxonomically diverse host range making it an excellent model system to study these processes. Here we analyze a global set of 901 genome sequences from nine diverse host species to advance our understanding of these processes. Bayesian clustering analysis delineated twelve major populations that closely aligned with niches. Comparative genomics revealed extensive gene gain/loss among populations and a large pan-genome of 9,527 genes, which remained open and was strongly partitioned among niches. As a result, the biochemical characteristics of eleven populations were highly distinctive (significantly enriched). Positive selection was detected and biochemical characteristics of the dispensable genes under selection were enriched in ten populations. Despite the strong gene partitioning, phylogenomics detected gene spillover. In particular, tetracycline resistance (which likely evolved in the human-associated population) from humans to bovine, canines, seals, and fish, demonstrating how a gene selected in one host can ultimately be transmitted into another, and biased transmission from humans to bovines was confirmed with a Bayesian migration analysis. Our findings show high bacterial genome plasticity acting in balance with selection pressure from distinct functional requirements of niches that is associated with an extensive and highly partitioned dispensable genome, likely facilitating continued and expansive adaptation

Stage-specific proteomes from onchocerca ochengi, sister species of the human river blindness parasite, uncover adaptations to a nodular lifestyle

Despite 40 years of control efforts, onchocerciasis (river blindness) remains one of the most important neglected tropical diseases, with 17 million people affected. The etiological agent, Onchocerca volvulus, is a filarial nematode with a complex lifecycle involving several distinct stages in the definitive host and blackfly vector. The challenges of obtaining sufficient material have prevented high-throughput studies and the development of novel strategies for disease control and diagnosis. Here, we utilize the closest relative of O. volvulus, the bovine parasite Onchocerca ochengi, to compare stage-specific proteomes and host-parasite interactions within the secretome. We identified a total of 4260 unique O. ochengi proteins from adult males and females, infective larvae, intrauterine microfilariae, and fluid from intradermal nodules. In addition, 135 proteins were detected from the obligate Wolbachia symbiont. Observed protein families that were enriched in all whole body extracts relative to the complete search database included immunoglobulin-domain proteins, whereas redox and detoxification enzymes and proteins involved in intracellular transport displayed stage-specific overrepresentation. Unexpectedly, the larval stages exhibited enrichment for several mitochondrial-related protein families, including members of peptidase family M16 and proteins which mediate mitochondrial fission and fusion. Quantification of proteins across the lifecycle using the Hi-3 approach supported these qualitative analyses. In nodule fluid, we identified 94 O. ochengi secreted proteins, including homologs of transforming growth factor-β and a second member of a novel 6-ShK toxin domain family, which was originally described from a model filarial nematode (Litomosoides sigmodontis). Strikingly, the 498 bovine proteins identified in nodule fluid were strongly dominated by antimicrobial proteins, especially cathelicidins. This first high-throughput analysis of an Onchocerca spp. proteome across the lifecycle highlights its profound complexity and emphasizes the extremely close relationship between O. ochengi and O. volvulus The insights presented here provide new candidates for vaccine development, drug targeting and diagnostic biomarkers

A genome-wide analysis of Escherichia coli responses to fosfomycin using TraDIS-Xpress reveals novel roles for phosphonate degradation and phosphate transport systems

BACKGROUND: Fosfomycin is an antibiotic that has seen a revival in use due to its unique mechanism of action and efficacy against isolates resistant to many other antibiotics. In Escherichia coli, fosfomycin often selects for loss-of-function mutations within the genes encoding the sugar importers, GlpT and UhpT. There has, however, not been a genome-wide analysis of the basis for fosfomycin susceptibility reported to date. METHODS: Here we used TraDIS-Xpress, a high-density transposon mutagenesis approach, to assay the role of all genes in E. coli involved in fosfomycin susceptibility. RESULTS: The data confirmed known fosfomycin susceptibility mechanisms and identified new ones. The assay was able to identify domains within proteins of importance and revealed essential genes with roles in fosfomycin susceptibility based on expression changes. Novel mechanisms of fosfomycin susceptibility that were identified included those involved in glucose metabolism and phosphonate catabolism (phnC-M), and the phosphate importer, PstSACB. The impact of these genes on fosfomycin susceptibility was validated by measuring the susceptibility of defined inactivation mutants. CONCLUSIONS: This work reveals a wider set of genes that contribute to fosfomycin susceptibility, including core sugar metabolism genes and two systems involved in phosphate uptake and metabolism previously unrecognized as having a role in fosfomycin susceptibility

Religious affiliation modulates weekly cycles of cropland burning in Sub-Saharan Africa

Research ArticleVegetation burning is a common land management practice in Africa, where fire is used for hunting, livestock husbandry, pest control, food gathering, cropland fertilization, and wildfire prevention. Given such strong anthropogenic control of fire, we tested the hypotheses that fire activity displays weekly cycles, and that the week day with the fewest fires depends on regionally predominant religious affiliation.We also analyzed the effect of land use (anthrome) on weekly fire cycle significance. Fire density (fire counts.km-2) observed per week day in each region was modeled using a negative binomial regression model, with fire counts as response variable, region area as offset and a structured random effect to account for spatial dependence. Anthrome (settled, cropland, natural, rangeland), religion (Christian, Muslim, mixed) week day, and their 2-way and 3-way interactions were used as independent variables. Models were also built separately for each anthrome, relating regional fire density with week day and religious affiliation. Analysis revealed a significant interaction between religion and week day, i.e. regions with different religious affiliation (Christian, Muslim) display distinct weekly cycles of burning. However, the religion vs. week day interaction only is significant for croplands, i.e. fire activity in African croplands is significantly lower on Sunday in Christian regions and on Friday in Muslim regions. Magnitude of fire activity does not differ significantly among week days in rangelands and in natural areas, where fire use is under less strict control than in croplands. These findings can contribute towards improved specification of ignition patterns in regional/global vegetation fire models, and may lead to more accurate meteorological and chemical weather forecastinginfo:eu-repo/semantics/publishedVersio