Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Nonparametric, Parametric and Semiparametric Models for Screening and Decoding Pools of Chemical Compounds

pounds are tested for potency with respect to one or more assays. In reality, only a very small fraction of the compounds in a collection will be potent enough to act as lead molecules in later drug discovery phases. Testing all compounds is neither cost-effective nor desirable. Based on the belief that chemical structure is highly related to potency of compounds, structure activity relationships (SARs) can be very helpful for selecting a handful of chemical compounds for testing. This work investigates SARs using four different statistical methods. The first uses a latent class cell-based method. The second benefits from a fractional factorial design for optimizing the cell-based method to significantly increase hit rates. The third improves HTS efficiency by considering pooling experiments for chemical compounds in the presence of interaction and dilution. Rather than testing one compound at a time, chemical compounds are mixed together and tested by groups. Likelihood models are built and hit rates are shown to be higher than for traditional methods. The fourth solves the estimation problem in a pooling experiment by treating the pooling data as missing at random. Semiparametric models are implemented and estimators are shown to be more efficient than likelihood methods based on the same data

Gene Expression Signatures of Energetic Acclimatisation in the Reef Building Coral Acropora millepora

Line K. Bay is with Australian Institute of Marine Science, Aurélie Guérécheau is with Australian Institute of Marine Science, Nikos Andreakis is with Australian Institute of Marine Science, Karin E. Ulstrup is with University of Copenhagen, Mikhail V. Matz is with UT Austin.Background -- Understanding the mechanisms by which natural populations cope with environmental stress is paramount to predict their persistence in the face of escalating anthropogenic impacts. Reef-building corals are increasingly exposed to local and global stressors that alter nutritional status causing reduced fitness and mortality, however, these responses can vary considerably across species and populations. -- Methodology/Principal Findings -- We compare the expression of 22 coral host genes in individuals from an inshore and an offshore reef location using quantitative Reverse Transcription-PCR (qRT-PCR) over the course of 26 days following translocation into a shaded, filtered seawater environment. Declines in lipid content and PSII activity of the algal endosymbionts (Symbiodinium ITS-1 type C2) over the course of the experiment indicated that heterotrophic uptake and photosynthesis were limited, creating nutritional deprivation conditions. Regulation of coral host genes involved in metabolism, CO2 transport and oxidative stress could be detected already after five days, whereas PSII activity took twice as long to respond. Opposing expression trajectories of Tgl, which releases fatty acids from the triacylglycerol storage, and Dgat1, which catalyses the formation of triglycerides, indicate that the decline in lipid content can be attributed, at least in part, by mobilisation of triacylglycerol stores. Corals from the inshore location had initially higher lipid content and showed consistently elevated expression levels of two genes involved in metabolism (aldehyde dehydrogenase) and calcification (carbonic anhydrase). -- Conclusions/Significance -- Coral host gene expression adjusts rapidly upon change in nutritional conditions, and therefore can serve as an early signature of imminent coral stress. Consistent gene expression differences between populations indicate that corals acclimatize and/or adapt to local environments. Our results set the stage for analysis of these processes in natural coral populations, to better understand the responses of coral communities to global climate change and to develop more efficient management strategies.Funding was provided by the Marine and Tropical Sciences Research Facility, the ARC Centre of Excellence for Coral Reef Studies and the Australian Institute of Marine Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o