ABC as a flexible framework to estimate demography over space and time: some cons,many pros

The analysis of genetic variation to estimate demographic and historical parameters and to quantitatively compare alternative scenarios recently gained a powerful and flexible approach: the Approximate Bayesian Computation (ABC). The likelihood functions does not need to be theoretically specified, but posterior distributions can be approximated by simulation even assuming very complex population models including both natural and human‐induced processes. Prior information can be easily incorporated and the quality of the results can be analysed with rather limited additional effort. ABC is not a statistical analysis per se, but rather a statistical framework and any specific application is a sort of hybrid between a simulation and a data‐analysis study. Complete software packages performing the necessary steps under a set of models and for specific genetic markers are already available, but the flexibility of the method is better exploited combining different programs. Many questions relevant in ecology can be addressed using ABC, but adequate amount of time should be dedicated to decide among alternative options and to evaluate the results. In this paper we will describe and critically comment on the different steps of an ABC analysis, analyse some of the published applications of ABC and provide user guidelines.     

Somatic and Dendritic Encoding of Spatial Variables in Retrosplenial Cortex Differs during 2D Navigation

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Leveraging whole genome sequencing data for demographic inference with approximate Bayesian computation

Accounting for historical demographic features, such as the strength and timing of gene flow and divergence times between closely related lineages, is vital for many inferences in evolutionary biology. Approximate Bayesian computation (ABC) is one method commonly used to estimate demographic parameters. However, the DNA sequences used as input for this method, often microsatellites or RADseq loci, usually represent a small fraction of the genome. Whole genome sequencing (WGS) data, on the other hand, have been used less often with ABC, and questions remain about the potential benefit of, and how to best implement, this type of data; we used pseudo‐observed data sets to explore such questions. Specifically, we addressed the potential improvements in parameter estimation accuracy that could be associated with WGS data in multiple contexts; namely, we quantified the effects of (a) more data, (b) haplotype‐based summary statistics, and (c) locus length. Compared with a hypothetical RADseq data set with 2.5 Mbp of data, using a 1 Gbp data set consisting of 100 Kbp sequences led to substantial gains in the accuracy of parameter estimates, which was mostly due to haplotype statistics and increased data. We also quantified the effects of including (a) locus‐specific recombination rates, and (b) background selection information in ABC analyses. Importantly, assuming uniform recombination or ignoring background selection had a negative effect on accuracy in many cases. Software and results from this method validation study should be useful for future demographic history analyses.     

Computation of pH evolution versus ionic products concentration in a fermentation broth

An algorithm developed for pH computation has been tested to calculate the theoretical pH changes in a culture medium during the course of a fermentation. A divergence between the computed pH value and the value measured with the electrode allows us to highlight the presence of undetected ionic products. The calculation with the algorithm by means of a computer requires only the knowledge of the ionic properties of the substrates and detected products and existing thermodynamic constants. (c) 1993 Wiley & Sons, Inc.     

采用Reichardt运动检测器和Boltzmann Machine神经网络的运动计算

建立了一个探讨灵长类视皮层从Ｖ１区到ＭＴ区的运动信息加工原理的计算模型,这个过程的突出特征是视觉运动信息经过了从局部检测进步到整体感知。模型的第一层由用于抽提运动模式的局部速度以及结构性质的Ｒｅｉｃｈａｒｄｔ运动检测器组成,进一步的加工是通过Ｂｏｌｔｚｍａｎｎ Ｍａｃｈｉｎｅ神经网络来实现的。这种网络的学习算法具有局部更新的显著性质,在学习阶段,网络不断地修改联结权重以形成对于记录在网络的显单元上     

Information contents and dinucleotide compositions of plant intron sequences vary with evolutionary origin

The DNA sequence composition of 526 dicot and 345 monocot intron sequences have been characterized using computational methods. Splice site information content and bulk intron and exon dinucleotide composition were determined. Positions 4 and 5 of 5 splice sites contain different statistically significant levels of information in the two groups. Basal levels of information in introns are higher in dicots than in monocots. Two dinucleotide groups, WW (AA, AU, UA, UU) and SS (CC, CG, GC, GG) have significantly different frequencies in exons and introns of the two plant groups. These results suggest that the mechanisms of splice-site recognition and binding may differ between dicot and monocot plants.     

Congruent population genetic structures and divergence histories in anther‐smut fungi and their host plants Silene italica and the Silene nutans species complex

Study of the congruence of population genetic structure between hosts and pathogens gives important insights into their shared phylogeographical and coevolutionary histories. We studied the population genetic structure of castrating anther‐smut fungi (genus Microbotryum) and of their host plants, the Silene nutans species complex, and the morphologically and genetically closely related Silene italica, which can be found in sympatry. Phylogeographical population genetic structure related to persistence in separate glacial refugia has been recently revealed in the S. nutans plant species complex across Western Europe, identifying several distinct lineages. We genotyped 171 associated plant–pathogen pairs of anther‐smut fungi and their host plant individuals using microsatellite markers and plant chloroplastic single nucleotide polymorphisms. We found clear differentiation between fungal populations parasitizing S. nutans and S. italica plants. The population genetic structure of fungal strains parasitizing the S. nutans plant species complex mirrored the host plant genetic structure, suggesting that the pathogen was isolated in glacial refugia together with its host and/or that it has specialized on the plant genetic lineages. Using random forest approximate Bayesian computation (ABC‐RF), we found that the divergence history of the fungal lineages on S. nutans was congruent with that previously inferred for the host plant and probably occurred with ancient but no recent gene flow. Genome sequences confirmed the genetic structure and the absence of recent gene flow between fungal genetic lineages. Our analyses of individual host–pathogen pairs contribute to a better understanding of co‐evolutionary histories between hosts and pathogens in natural ecosystems, in which such studies remain scarce.     

Genetic diversity,structure, and demography of Pandanus boninensis (Pandanaceae) with sea drifted seeds,endemic to the Ogasawara Islands of Japan: Comparison between young and old islands

Pandanus boninensis, endemic to the Ogasawara Islands, Japan, is distributed on both the older Bonin and younger Volcano Islands. In this study, we conducted population genetic analyses of P. boninensis on these islands to examine the population diversity and structure across old and young islands, to assess potential differences in population demography with island age, and to collect any evidence of migration between old and young islands. We found that the genetic diversity of expressed sequence tag (EST)–based microsatellite (SSR) markers, the nucleotide diversity of nuclear DNA sequences, and the haplotype diversity of chloroplast DNA on young islands were lower than those on old islands. Clustering analyses of EST‐SSR indicated that populations on old islands were strongly diverged from those on young islands. Approximate Bayesian computation analysis of EST‐SSR suggested that population expansion occurred on old islands while population reduction occurred on young islands. We also found evidence of migration among old islands (mostly from south to north), while it appears that there have been very few migration events between old and young islands. These differences could be due to the fact that young islands tend to be geographically isolated and support smaller populations that began a shorter time ago from limited founders. The P. boninensis populations on the Volcano Islands are interesting from an evolutionary perspective as they constitute a classic example of the early stages of progressive colonization on oceanic islands with small effective population sizes and low genetic diversity.     

Genetic variation in Plethodon cinereus and Plethodon hubrichti from in and around a contact zone

Climate change poses several challenges to biological communities including changes in the frequency of encounters between closely related congeners as a result of range shifts. When climate change leads to increased hybridization, hybrid dysfunction or genetic swamping may increase extinction risk—particularly in range‐restricted species with low vagility. The Peaks of Otter Salamander, Plethodon hubrichti, is a fully terrestrial woodland salamander that is restricted to ~18 km of ridgeline in the mountains of southwestern Virginia, and its range is surrounded by the abundant and widespread Eastern Red‐backed Salamander, Plethodon cinereus. In order to determine whether these two species are hybridizing and how their range limits may be shifting, we assessed variation at eight microsatellite loci and a 1,008 bp region of Cytochrome B in both species at allopatric reference sites and within a contact zone. Our results show that hybridization between P. hubrichti and P. cinereus either does not occur or is very rare. However, we find that diversity and differentiation are substantially higher in the mountaintop endemic P. hubrichti than in the widespread P. cinereus, despite similar movement ability for the two species as assessed by a homing experiment. Furthermore, estimation of divergence times between reference and contact zone populations via approximate Bayesian computation is consistent with the idea that P. cinereus has expanded into the range of P. hubrichti. Given the apparent recent colonization of the contact zone by P. cinereus, future monitoring of P. cinereus range limits should be a priority for the management of P. hubrichti populations.     

Adjustment for exploratory cut-off selection in randomized clinical trials with survival endpoint

Defining the target population based on predictive biomarkers plays an important role during clinical development. After establishing a relationship between a biomarker candidate and response to treatment in exploratory phases, a subsequent confirmatory trial ideally involves only subjects with high potential of benefiting from the new compound. In order to identify those subjects in case of a continuous biomarker, a cut-off is needed. Usually, a cut-off is chosen that resulted in a subgroup with a large observed treatment effect in an exploratory trial. However, such a data-driven selection may lead to overoptimistic expectations for the subsequent confirmatory trial. Treatment effect estimates, probability of success, and posterior probabilities are useful measures for deciding whether or not to conduct a confirmatory trial enrolling the biomarker-defined population. These measures need to be adjusted for selection bias. We extend previously introduced Approximate Bayesian Computation techniques for adjustment of subgroup selection bias to a time-to-event setting with cut-off selection. Challenges in this setting are that treatment effects become time-dependent and that subsets are defined by the biomarker distribution. Simulation studies show that the proposed method provides adjusted statistical measures which are superior to naïve Maximum Likelihood estimators as well as simple shrinkage estimators.