Sequencing impact at the University of Missouri

Executive Summary: It would be an understatement to say that "next-generation" sequencing technology has been revolutionary. Over the last 10 years, sequencing has created a paradigm shift in biological sciences where more and more a component of research involves "just sequence it". This is because the types of data, applications and resulting insights are expanding every year. Further, the volume and speed of data generation are growing exponentially, while the costs to generate these data are decreasing exponentially. The Human Genome Project completed the first draft genome sequence in 2001 at an estimated cost of $3 billion. Next-generation sequencing became mainstream around 2007 and enabled the re-sequencing of a human genome at a cost of approximately$50,000. In late 2015, Illumina announced the availability of their X10 sequencer for use on non-human samples enabling the re-sequencing of a mammalian (human, cow, dog etc.) genome for approximately $1,500 and with an annual throughput of 10,000 genomes per year. The ease, rapidity and cost effectiveness of generating sequence data has created a computational analysis bottleneck. The growth of computational resources on the MU campus has not kept pace with the growth in data generation capability. In order for Mizzou to maintain a competitive research environment, we need to expand the computational resources available for bioinformatics analysis of large data which include sequence data. It will require an initial investment of$619,000 in early 2016 to build the needed core infrastructure and will require ongoing funding to maintain and expand this infrastructure. Initial investments (cost share of $231,000) made by Mizzou in 2005 to bring next-generation sequencing to this campus have been returned many-fold. Based on a survey sent to MU researchers in November 2015, a total of 66 grants have been awarded involving sequencing for a total of$87.5M. $7.6M of that is directly attributable to sequence data generation/analysis. In addition, another$7.9M in grant funding has been submitted and remains pending. This research has led to 173 refereed journal articles in top-tier journals producing over 6,000 citations. Additionally, 19 M.S., 62 Ph.D. and 21 postdocs have been trained as a result of these sequence related research projects. Plant and animal researchers at MU have been at the forefront of the next-generation sequencing revolution. However, based on the diversity of grants and papers gathered by the survey, sequence analysis provides a common foundation that ties together many disciplines on campus. As such, investment in computational capacity directed at sequence data analysis will serve the entire campus and provide technological ties between disciplines. The following is a detailed description of the history of sequencing/bioinformatics, a description of the computation resources required, and a model for sustainability and an analysis of the impacts of next-generation sequencing at Mizzou

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p

Genome-wide association study for feed efficiency and growth traits in U.S. beef cattle

Background: Single nucleotide polymorphism (SNP) arrays for domestic cattle have catalyzed the identification of genetic markers associated with complex traits for inclusion in modern breeding and selection programs. Using actual and imputed Illumina 778K genotypes for 3887 U.S. beef cattle from 3 populations (Angus, Hereford, SimAngus), we performed genome-wide association analyses for feed efficiency and growth traits including average daily gain (ADG), dry matter intake (DMI), mid-test metabolic weight (MMWT), and residual feed intake (RFI), with marker-based heritability estimates produced for all traits and populations. Results: Moderate and/or large-effect QTL were detected for all traits in all populations, as jointly defined by the estimated proportion of variance explained (PVE) by marker effects (PVE ≥ 1.0%) and a nominal P-value threshold (P ≤ 5e-05). Lead SNPs with PVE ≥ 2.0% were considered putative evidence of large-effect QTL (n = 52), whereas those with PVE ≥ 1.0% but \u3c 2.0% were considered putative evidence for moderate-effect QTL (n = 35). Identical or proximal lead SNPs associated with ADG, DMI, MMWT, and RFI collectively supported the potential for either pleiotropic QTL, or independent but proximal causal mutations for multiple traits within and between the analyzed populations. Marker-based heritability estimates for all investigated traits ranged from 0.18 to 0.60 using 778K genotypes, or from 0.17 to 0.57 using 50K genotypes (reduced from Illumina 778K HD to Illumina Bovine SNP50). An investigation to determine if QTL detected by 778K analysis could also be detected using 50K genotypes produced variable results, suggesting that 50K analyses were generally insufficient for QTL detection in these populations, and that relevant breeding or selection programs should be based on higher density analyses (imputed or directly ascertained). Conclusions: Fourteen moderate to large-effect QTL regions which ranged from being physically proximal (lead SNPs ≤ 3Mb) to fully overlapping for RFI, DMI, ADG, and MMWT were detected within and between populations, and included evidence for pleiotropy, proximal but independent causal mutations, and multi-breed QTL. Bovine positional candidate genes for these traits were functionally conserved across vertebrate species

Mitgliederrückgang und Organisationsstrategien deutscher Gewerkschaften

Die deutschen Gewerkschaften kommen zunehmend unter existentiellen Druck: Der vereinigungsbedingte Boom von vier Millionen Mitgliedern im Osten ist innerhalb eines Jahrzehntes zerronnen und im Westen setzt sich die – seit den 1980er Jahren herrschende – Erosion der Mitgliederbasis fort. Heute sind weniger Arbeitnehmer gewerkschaftlich organisiert als je zuvor in der Geschichte der Bundesrepublik. Der Tiefstand der Weimarer Republik ist bereits unterschritten: Nur jeder sechste Arbeitnehmer, der noch nicht im (Vor-)Ruhestand ist, zahlt einen Gewerkschaftsbeitrag, während die große Mehrheit der Nichtmitglieder auch von Tarifverträgen profitieren, die von den Gewerkschaften mit den Arbeitgebern ausgehandelt werden

Greenhouse gas mitigation in agriculture

Agricultural lands occupy 37% of the earth's land surface. Agriculture accounts for 52 and 84% of global anthropogenic methane and nitrous oxide emissions. Agricultural soils may also act as a sink or source for CO2, but the net flux is small. Many agricultural practices can potentially mitigate greenhouse gas (GHG) emissions, the most prominent of which are improved cropland and grazing land management and restoration of degraded lands and cultivated organic soils. Lower, but still significant mitigation potential is provided by water and rice management, set-aside, land use change and agroforestry, livestock management and manure management. The global technical mitigation potential from agriculture (excluding fossil fuel offsets from biomass) by 2030, considering all gases, is estimated to be approximately 5500–6000 Mt CO2-eq. yr−1, with economic potentials of approximately 1500–1600, 2500–2700 and 4000–4300 Mt CO2-eq. yr−1 at carbon prices of up to 20, up to 50 and up to 100 US$t CO2-eq.−1, respectively. In addition, GHG emissions could be reduced by substitution of fossil fuels for energy production by agricultural feedstocks (e.g. crop residues, dung and dedicated energy crops). The economic mitigation potential of biomass energy from agriculture is estimated to be 640, 2240 and 16 000 Mt CO2-eq. yr−1 at 0–20, 0–50 and 0–100 US$ t CO2-eq.−1, respectively