Yeast Features: Identifying Significant Features Shared Among Yeast Proteins for Functional Genomics

Background
High throughput yeast functional genomics experiments are revealing associations among tens to hundreds of genes using numerous experimental conditions. To fully understand how the identified genes might be involved in the observed system, it is essential to consider the widest range of biological annotation possible. Biologists often start their search by collating the annotation provided for each protein within databases such as the Saccharomyces Genome Database, manually comparing them for similar features, and empirically assessing their significance. Such tasks can be automated, and more precise calculations of the significance can be determined using established probability measures. 
Results
We developed Yeast Features, an intuitive online tool to help establish the significance of finding a diverse set of shared features among a collection of yeast proteins. A total of 18,786 features from the Saccharomyces Genome Database are considered, including annotation based on the Gene Ontology’s molecular function, biological process and cellular compartment, as well as conserved domains, protein-protein and genetic interactions, complexes, metabolic pathways, phenotypes and publications. The significance of shared features is estimated using a hypergeometric probability, but novel options exist to improve the significance by adding background knowledge of the experimental system. For instance, increased statistical significance is achieved in gene deletion experiments because interactions with essential genes will never be observed. We further demonstrate the utility by suggesting the functional roles of the indirect targets of an aminoglycoside with a known mechanism of action, and also the targets of an herbal extract with a previously unknown mode of action. The identification of shared functional features may also be used to propose novel roles for proteins of unknown function, including a role in protein synthesis for YKL075C.
Conclusions
Yeast Features (YF) is an easy to use web-based application (http://software.dumontierlab.com/yeastfeatures/) which can identify and prioritize features that are shared among a set of yeast proteins. This approach is shown to be valuable in the analysis of complex data sets, in which the extracted associations revealed significant functional relationships among the gene products.
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Science-based conservation and management in wetland archaeology: the example of Sutton Common, UK

Reproduced with permission of the publisher. © Oxbow Books and the individual auhtors, 2001. Details of the publication are available at: http://www.oxbowbooks.com/bookinfo.cfm/ID/3080

An assessment of the potential for in situ preservation of buried organic archaeological remains at Sutton Common, South Yorkshire

The broad aim of this research was to develop a methodological approach to the monitoring of archaeological sites that contained, or had the potential to contain, well-preserved organic archaeological remains, by means of a multidisciplinary approach. Such sites could generally be referred to as wetland archaeological sites, as material is preserved as a function of an existing or former wetland environment. Such an approach would provide high quality data from different sources that could be considered mutually supportive, generating information that could therefore be considered reliable. The more specific aims of the research can be considered as:1. To develop a monitoring package that can effectively and accurately identify conditions that are conducive to the long-term preservation of organic archaeological materials, specifically wood.2. To understand in detail the burial dynamics of Sutton Common.3. To identify the changes within the burial environment on Sutton Common that occurred as a direct consequence of activities aimed at raising the watertable and to assess whether these aided the potential for in situ preservation.Of significance is the amount and quality of the data collected, with the techniques used generating high resolution data over an extended period of time. Such data concerning the burial environment has not previously been collated to such an extent.To satisfy these three specific aims, a monitoring approach was chosen that made use of multiple factors; these being hydrological monitoring, soil redox monitoring and microbiological assessment. The most crucial of these, and the one that has been the focus of the monitoring effort, has been the hydrological monitoring as this is essential at identifying saturated conditions, which are the basic conditions required for good preservation. Soil redox monitoring closely supported this by being capable of identifying anaerobic conditions that indicate stable conditions, ideal for preservation. As soil redox monitoring requires more resources in terms of time and funds, this variable has not been as widely implemented as the piezometer grid installed for hydrological monitoring. Such factors have also influenced the implementation of microbial techniques on Sutton Common, with these being applied as an assessment, and a means of gathering baseline data, rather than a monitoring variable proper.The presentation of these techniques and the specific methods used have been detailed in Chapter 3, with the results of the monitoring programme for each of the approaches being presented in Chapters 5, 6 and 7 in the context of previous monitoring exercises and published literature. The significant findings were discussed and specific reference made to the impact of flooding on Sutton Common and the influence of re-wetting activities in Chapter 8.The concluding chapter summarises the main findings of each of the three disciplines studied along with the findings obtained from the analysis of the flooding event of 2000/01, and the effects of the drainage mitigation implemented on Sutton Common. These are then related to the original aims set out in Chapter 1, followed by the wider implications of this research and the main recommendations arising from it

Performance of the Gemini Planet Imager Non-Redundant Mask and spectroscopy of two close-separation binaries HR 2690 and HD 142527

The Gemini Planet Imager (GPI) contains a 10-hole non-redundant mask (NRM), enabling interferometric resolution in complement to its coronagraphic capabilities. The NRM operates both in spectroscopic (integral field spectrograph, henceforth IFS) and polarimetric configurations. NRM observations were taken between 2013 and 2016 to characterize its performance. Most observations were taken in spectroscopic mode with the goal of obtaining precise astrometry and spectroscopy of faint companions to bright stars. We find a clear correlation between residual wavefront error measured by the AO system and the contrast sensitivity by comparing phase errors in observations of the same source, taken on different dates. We find a typical 5-$\sigma$ contrast sensitivity of $2-3~\times~10^{-3}$ at $\sim\lambda/D$. We explore the accuracy of spectral extraction of secondary components of binary systems by recovering the signal from a simulated source injected into several datasets. We outline data reduction procedures unique to GPI's IFS and describe a newly public data pipeline used for the presented analyses. We demonstrate recovery of astrometry and spectroscopy of two known companions to HR 2690 and HD 142527. NRM+polarimetry observations achieve differential visibility precision of $\sigma\sim0.4\%$ in the best case. We discuss its limitations on Gemini-S/GPI for resolving inner regions of protoplanetary disks and prospects for future upgrades. We summarize lessons learned in observing with NRM in spectroscopic and polarimetric modes.Comment: Accepted to AJ, 22 pages, 14 figure

An ancient founder mutation in PROKR2 impairs human reproduction

Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutation's age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same ∼123 kb haplotype whose population frequency is ≤10%. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproductio

A Proximity Complementation Assay to Identify Small Molecules That Enhance the Traffic of ABCA4 Misfolding Variants

ABCA4-related retinopathy is the most common inherited Mendelian eye disorder worldwide, caused by biallelic variants in the ATP-binding cassette transporter ABCA4. To date, over 2200 ABCA4 variants have been identified, including missense, nonsense, indels, splice site and deep intronic defects. Notably, more than 60% are missense variants that can lead to protein misfolding, mistrafficking and degradation. Currently no approved therapies target ABCA4. In this study, we demonstrate that ABCA4 misfolding variants are temperature-sensitive and reduced temperature growth (30 °C) improves their traffic to the plasma membrane, suggesting the folding of these variants could be rescuable. Consequently, an in vitro platform was developed for the rapid and robust detection of ABCA4 traffic to the plasma membrane in transiently transfected cells. The system was used to assess selected candidate small molecules that were reported to improve the folding or traffic of other ABC transporters. Two candidates, 4-PBA and AICAR, were identified and validated for their ability to enhance both wild-type ABCA4 and variant trafficking to the cell surface in cell culture. We envision that this platform could serve as a primary screen for more sophisticated in vitro testing, enabling the discovery of breakthrough agents to rescue ABCA4 protein defects and mitigate ABCA4-related retinopathy