Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project

The Alzheimer's Disease Sequencing Project (ADSP) performed whole genome sequencing (WGS) of 584 subjects from 111 multiplex families at three sequencing centers. Genotype calling of single nucleotide variants (SNVs) and insertion-deletion variants (indels) was performed centrally using GATK-HaplotypeCaller and Atlas V2. The ADSP Quality Control (QC) Working Group applied QC protocols to project-level variant call format files (VCFs) from each pipeline, and developed and implemented a novel protocol, termed “consensus calling,” to combine genotype calls from both pipelines into a single high-quality set. QC was applied to autosomal bi-allelic SNVs and indels, and included pipeline-recommended QC filters, variant-level QC, and sample-level QC. Low-quality variants or genotypes were excluded, and sample outliers were noted. Quality was assessed by examining Mendelian inconsistencies (MIs) among 67 parent-offspring pairs, and MIs were used to establish additional genotype-specific filters for GATK calls. After QC, 578 subjects remained. Pipeline-specific QC excluded ~12.0% of GATK and 14.5% of Atlas SNVs. Between pipelines, ~91% of SNV genotypes across all QCed variants were concordant; 4.23% and 4.56% of genotypes were exclusive to Atlas or GATK, respectively; the remaining ~0.01% of discordant genotypes were excluded. For indels, variant-level QC excluded ~36.8% of GATK and 35.3% of Atlas indels. Between pipelines, ~55.6% of indel genotypes were concordant; while 10.3% and 28.3% were exclusive to Atlas or GATK, respectively; and ~0.29% of discordant genotypes were. The final WGS consensus dataset contains 27,896,774 SNVs and 3,133,926 indels and is publicly available.     

Lymphokine and phorbol (PMA) regulation of complement (C2) synthesis using U937

Human monocytes synthesize large amounts of the second complement component (C2) after incubation with a T-lymphocyte product called monocyte complement stimulator (MCS). The human monocyte-like cell line, U937, also synthesizes C2 and can be stimulated to increase this synthesis by lymphokine-rich culture supernates. Additionally, phorbol myristate acetate (PMA), an agent which induces maturational changes in other macrophage-like cell lines, also stimulates C2 synthesis by U937 cells. Lymphokine and PMA stimulation of C2 secretion by U937 are both reversibly inhibitable by cycloheximide. At optimal concentrations for stimulation of C2 synthesis, PMA inhibits [³H]thymidine incorporation by U937 indicating that increased C2 is not due to increased numbers of U937 cells.     

Long-Term Changes of a Coastal Bird Breeding Community on a Small Island – Does Natural Succession Compromise Conservation Values?

Limited spatial resources available for conservation lead to controversy about whether to apply single-species management or ecosystemary approaches in order to maintain biodiversity. In this study I analyse changes in a community of breeding coastal birds over a 90-year period, in order to examine whether natural processes on an unmanaged island are in accordance with requirements to save endangered species. Both diversity and species richness of the community increased significantly over time, and evenness increased after having been severely reduced by human impact. Diversity, evenness and species richness seemed to approach an equilibrium in the past decade, but number of breeding pairs declined as a consequence of altered natural disturbance regime. Species identity changed over time, with two initially very common species recently becoming locally extinct. These species are of high conservation concern, and their disappearance causes a problem for the concept of naturalness on islands. I conclude that natural processes need to be applied to the entire landscape in order to maintain dynamic processes that are essential for the survival of these species. The natural changes on the island should not be interrupted, but rather demonstrated to the public in order to increase conservation mindedness and gain support for changes in anthropogenic influences on a larger spatial scale.     

Marine ecosystem dynamics: Comparison of scales

When marine and terrestrial ecological systems are compared at the same time scales, there are very great differences in their relations with their physical environments. Similarities arise when comparisons are made at different time scales. There are significant consequences for management.     

Valuing mangrove ecosystem services: linking nutrient retention function of mangrove forests to enhanced agroecosystem production

Mangroves are highly productive wetland ecosystems strategically located at the interface between land and sea. They play an important role in the biogeochemical cycles of the coastal environment, acting as sources of nutrients to adjacent marine and terrestrial ecosystems through active and passive transport. We examined the nutrient contents in mangrove and nonmangrove soils in and around the Bhitarkanika National Park, India and assessed whether the local agricultural producers were aware of and placed a value on this contribution of mangrove forests in enhancing agroecosystem productivity. Soil samples from both mangrove and nonmangrove areas were analysed and quantity of organic carbon, total nitrogen, available phosphorus and potassium were derived. The replacement cost method was used to derive the value of nutrients in mangrove soils. We estimated that each hectare of mangrove contains additional nutrients worth US$232.49 in comparison to nonmangrove areas. The difference in nutrient content in mangrove versus nonmangrove areas gave the value of US$3.37 million for the nutrients in 145 km² of mangrove forests. The agricultural producers were aware that mangrove forests act as a source of nutrients and were willing to pay a higher price for the land adjoining mangrove forests. Around 92% of the producers ranked nutrient retention as a secondary function of mangrove forests. Despite crop depredation from wild ungulates and conflict with salt water crocodiles the agriculturist finds the benefit to cost ratio of mangrove forests high and more than 76% were in favour of mangrove restoration. This study provides an opportunity to highlight the importance of mangrove ecosystems to the livelihoods of the local people and the urgent need to sustain these through proper policy and market interventions.     

一类具稀疏效应生态系统的极限环

研究如下一类具稀疏效应的生态系统模型dx/dt=bx^2(κ-x)-bxy/1 hx,dy/dt=cy dxy/1 hx。应用微分方程定性理论,对该系统的平衡点进行了分析,给出了极限环存在唯一性及不存在的参数范围。     

Linking bioprospecting with sustainable development and conservation: the Panama case

The limited international resources for economic aid and conservation can only mitigate poverty and losses of biodiversity. Hence, developing nations must establish the capacity to resolve their problems. Additionally, policy-makers and donors need to obtain scientific input on issues such as global change and ecosystem services. We propose that for nations rich in biodiversity, ecosystem services derived from bioprospecting, or drug discovery, could contribute to economic development. In the case where unstudied samples are shipped abroad for research, the chances of obtaining royalties are infinitesimally small. Therefore developing nations will only realize benefits from bioprospecting through in-country research on their own biodiversity. Policy-makers and donors have failed to appreciate the value of this approach. In order to provide an example of the inherent links between conservation and sustainable economic development, we initiated a drug discovery effort in Panama that emphasizes local benefit. As much of the drug discovery process as possible is conducted in Panamanian laboratories, providing jobs dependent on intact biodiversity and enhancing local research and training. In short, research, plus the spin-offs from research, provide immediate and long-lasting benefits to Panama. The connection between conservation and development has been highlighted in publicity about the project in Panama’s urban media. This provides a constructive alternative to the perception the among the urban populace that economic development inevitably competes with conservation. In summary, our program uses biodiversity to promote human health as well as to support research capacity, economic development and conservation within Panama. The program provides an example of the widely recognized but little developed concept of bioprospecting research as an ecosystem service.