The distribution of maxima of approximately Gaussian random fields

Motivated by the problem of testing for the existence of a signal of known parametric structure and unknown ``location'' (as explained below) against a noisy background, we obtain for the maximum of a centered, smooth random field an approximation for the tail of the distribution. For the motivating class of problems this gives approximately the significance level of the maximum score test. The method is based on an application of a likelihood-ratio-identity followed by approximations of local fields. Numerical examples illustrate the accuracy of the approximations.Comment: Published in at http://dx.doi.org/10.1214/07-AOS511 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Detecting simultaneous variant intervals in aligned sequences

Given a set of aligned sequences of independent noisy observations, we are concerned with detecting intervals where the mean values of the observations change simultaneously in a subset of the sequences. The intervals of changed means are typically short relative to the length of the sequences, the subset where the change occurs, the "carriers," can be relatively small, and the sizes of the changes can vary from one sequence to another. This problem is motivated by the scientific problem of detecting inherited copy number variants in aligned DNA samples. We suggest a statistic based on the assumption that for any given interval of changed means there is a given fraction of samples that carry the change. We derive an analytic approximation for the false positive error probability of a scan, which is shown by simulations to be reasonably accurate. We show that the new method usually improves on methods that analyze a single sample at a time and on our earlier multi-sample method, which is most efficient when the carriers form a large fraction of the set of sequences. The proposed procedure is also shown to be robust with respect to the assumed fraction of carriers of the changes.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS400 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Scanning a Poisson Random Field for Local Signals

The detection of local genomic signals using high-throughput DNA sequencing data can be cast as a problem of scanning a Poisson random field for local changes in the rate of the process. We propose a likelihood-based framework for such scans, and derive formulas for false positive rate control and power calculations. The framework can also accommodate modified processes that involve overdispersion. As a specific, detailed example, we consider the detection of insertions and deletions by paired-end DNA-sequencing. We propose several statistics for this problem, compare their power under current experimental designs, and illustrate their application on an Illumina Platinum Genomes data set

Vapour pressure deficit was not a primary limiting factor for gas exchange in an irrigated, mature dryland Aleppo pine forest

Climate change is often associated with increasing vapour pressure deficit (VPD) and changes in soil moisture (SM). While atmospheric and soil drying often co-occur, their differential effects on plant functioning and productivity remain uncertain. We investigated the divergent effects and underlying mechanisms of soil and atmospheric drought based on continuous, in situ measurements of branch gas exchange with automated chambers in a mature semiarid Aleppo pine forest. We investigated the response of control trees exposed to combined soil‒atmospheric drought (low SM, high VPD) during the rainless Mediterranean summer and that of trees experimentally unconstrained by soil dryness (high SM; using supplementary dry season water supply) but subjected to atmospheric drought (high VPD). During the seasonal dry period, branch conductance (g$_{br}$), transpiration rate (E) and net photosynthesis (A$_{net}$) decreased in low-SM trees but greatly increased in high-SM trees. The response of E and g$_{br}$ to the massive rise in VPD (to 7 kPa) was negative in low-SM trees and positive in high-SM trees. These observations were consistent with predictions based on a simple plant hydraulic model showing the importance of plant water potential in the g$_{br}$ and E response to VPD. These results demonstrate that avoiding drought on the supply side (SM) and relying on plant hydraulic regulation constrains the effects of atmospheric drought (VPD) as a stressor on canopy gas exchange in mature pine trees under field conditions

Assessing model performance via the most limiting environmental driver in two differently stressed pine stands

Climate change will impact forest productivity worldwide. Forecasting the magnitude of such impact, with multiple environmental stressors changing simultaneously, is only possible with the help of process-based models. In order to assess their performance, such models require careful evaluation against measurements. However, direct comparison of model outputs against observational data is often not reliable, as models may provide the right answers due to the wrong reasons. This would severely hinder forecasting abilities under unprecedented climate conditions. Here, we present a methodology for model assessment, which supplements the traditional output-to-observation model validation. It evaluates model performance through its ability to reproduce observed seasonal changes of the most limiting environmental driver (MLED) for a given process, here daily gross primary productivity (GPP). We analyzed seasonal changes of the MLED for GPP in two contrasting pine forests, the Mediterranean Pinus halepensis Mill. Yatir (Israel) and the boreal Pinus sylvestris L. Hyytiala (Finland) from three years of eddy-covariance flux data. Then, we simulated the same period with a state-of-the-art process-based simulation model (LandscapeDNDC). Finally, we assessed if the model was able to reproduce both GPP observations and MLED seasonality. We found that the model reproduced the seasonality of GPP in both stands, but it was slightly overestimated without site-specific fine-tuning. Interestingly, although LandscapeDNDC properly captured the main MLED in Hyytiala (temperature) and in Yatir (soil water availability), it failed to reproduce high-temperature and high-vapor pressure limitations of GPP in Yatir during spring and summer. We deduced that the most likely reason for this divergence is an incomplete description of stomatal behavior. In summary, this study validates the MLED approach as a model evaluation tool, and opens up new possibilities for model improvement.Peer reviewe

Hot drought reduces the effects of elevated CO₂ on tree water use efficiency and carbon metabolism

- Trees are increasingly exposed to hot droughts due to CO2-induced climate change. However, the direct role of [CO2] in altering tree physiological responses to drought and heat stress remains ambiguous. - Pinus halepensis (Aleppo pine) trees were grown from seed under ambient (421 ppm) or elevated (867 ppm) [CO2]. The 1.5-yr-old trees, either well watered or drought treated for 1 month, were transferred to separate gas-exchange chambers and the temperature gradually increased from 25°C to 40°C over a 10 d period. Continuous whole-tree shoot and root gasexchange measurements were supplemented by primary metabolite analysis. - Elevated [CO2] reduced tree water loss, reflected in lower stomatal conductance, resulting in a higher water-use efficiency throughout amplifying heat stress. Net carbon uptake declined strongly, driven by increases in respiration peaking earlier in the well-watered (31– 32°C) than drought (33–34°C) treatments unaffected by growth [CO2]. Further, drought altered the primary metabolome, whereas the metabolic response to [CO2] was subtle and mainly reflected in enhanced root protein stability. - The impact of elevated [CO2] on tree stress responses was modest and largely vanished with progressing heat and drought. We therefore conclude that increases in atmospheric [CO2] cannot counterbalance the impacts of hot drought extremes in Aleppo pine

Anatomical adjustments of the tree hydraulic pathway decrease canopy conductance under long-term elevated CO2_2

The cause of reduced leaf-level transpiration under elevated CO$_2$ remains largely elusive. Here, we assessed stomatal, hydraulic, and morphological adjustments in a long-term experiment on Aleppo pine (Pinus halepensis) seedlings germinated and grown for 22–40 months under elevated (eCO$_2$; c. 860 ppm) or ambient (aCO$_2$; c. 410 ppm) CO$_2$. We assessed if eCO$_2$-triggered reductions in canopy conductance (g$_c$) alter the response to soil or atmospheric drought and are reversible or lasting due to anatomical adjustments by exposing eCO$_2$ seedlings to decreasing [CO$_2$]. To quantify underlying mechanisms, we analyzed leaf abscisic acid (ABA) level, stomatal and leaf morphology, xylem structure, hydraulic efficiency, and hydraulic safety. Effects of eCO$_2$ manifested in a strong reduction in leaf-level g$_c$ (−55%) not caused by ABA and not reversible under low CO$_2$ (c. 200 ppm). Stomatal development and size were unchanged, while stomatal density increased (+18%). An increased vein-to-epidermis distance (+65%) suggested a larger leaf resistance to water flow. This was supported by anatomical adjustments of branch xylem having smaller conduits (−8%) and lower conduit lumen fraction (−11%), which resulted in a lower specific conductivity (−19%) and leaf-specific conductivity (−34%). These adaptations to CO$_2$ did not change stomatal sensitivity to soil or atmospheric drought, consistent with similar xylem safety thresholds. In summary, we found reductions of g$_c$ under elevated CO$_2$ to be reflected in anatomical adjustments and decreases in hydraulic conductivity. As these water savings were largely annulled by increases in leaf biomass, we do not expect alleviation of drought stress in a high CO$_2$ atmosphere

Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights

Genome-wide association studies (GWAS) have identified over 100 risk loci for schizophrenia, but the causal mechanisms remain largely unknown. We performed a transcriptome-wide association study (TWAS) integrating a schizophrenia GWAS of 79,845 individuals from the Psychiatric Genomics Consortium with expression data from brain, blood, and adipose tissues across 3,693 primarily control individuals. We identified 157 TWAS-significant genes, of which 35 did not overlap a known GWAS locus. Of these 157 genes, 42 were associated with specific chromatin features measured in independent samples, thus highlighting potential regulatory targets for follow-up. Suppression of one identified susceptibility gene, mapk3, in zebrafish showed a significant effect on neurodevelopmental phenotypes. Expression and splicing from the brain captured most of the TWAS effect across all genes. This large-scale connection of associations to target genes, tissues, and regulatory features is an essential step in moving toward a mechanistic understanding of GWAS