Automating Reproducibility - Challenges and what it takes to meet them

Computational reproducibility is a building block for transparent and cumulative science. It enables the originator and other researchers, on other computers and later in time, to reproduce and thus understand how results came about while avoiding various errors that may lead to erroneous reporting of statistical and computational results. But what does it take to make something reproducible? Until recently, detailed descriptions of methods and analyses were the primary instrument for ensuring scientific reproducibility. Such manual description fails to ensure reproduction due to four different reasons that get more likely the more central computational methods are for research. To meet these challenges, we propose that researchers take advantage of four technological advancements—version control, dynamic document generation, workflow automation, and containerization. Our workflow enables scientists to achieve a more comprehensive standard that allows anyone to access a digital research repository and reproduce all computational steps from raw data to final report with a single command

Grain Yield Stability of Cereal-Legume Intercrops Is Greater Than Sole Crops in More Productive Conditions

The intercropping of two or more crop species on the same piece of land at a given time has been hypothesized to enhance crop yield stability. To address this hypothesis, we assessed the grain yield stability of various barley-pea and wheat-faba bean mixtures grown in seven experimental field trials (locations) across Europe during two years with contrasting weather (2017 and 2018). Three different yield stability measures were used, all based on the expected yield variability of the mixture components grown as sole crops, and the corresponding observed yield variability of the same components grown in 50:50 mixtures in a replacement design. Stability indices were calculated as ratios between the expected and observed variabilities, with values > 1 indicating greater stability of the intercrops. Mean grain yields tended to be higher in intercrops than sole crops. However, in contrast to our hypothesis, the observed (intercrop) yield stability was similar or lower than the expected (sole crop) stability in most locations except one. Furthermore, yield stability significantly increased with increasing mean yields when assessed across differentially productive locations. The results are relevant for the designing of intercropping systems as a means to increase yield stability and the resilience of cropping systems.This research was funded by the DIVERSify project, a grant from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 727284. MR was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—420661662. A.J.K. and A.C.N. are also supported by the strategic research programme funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division.Peer reviewe

Negative feedback regulation of MAPK signaling is an important driver of chronic lymphocytic leukemia progression

Despite available targeted treatments for the disease, drug-resistant chronic lymphocytic leukemia (CLL) poses a clinical challenge. The objective of this study is to examine whether the dual-specific phosphatases DUSP1 and DUSP6 are required to negatively regulate mitogen-activated protein kinases (MAPKs) and thus counterbalance excessive MAPK activity. We show that high expression of DUSP6 in CLL correlates with poor clinical prognosis. Importantly, genetic deletion of the inhibitory phosphatase DUSP1 or DUSP6 and blocking DUSP1/6 function using a small-molecule inhibitor reduces CLL cell survival in vitro and in vivo. Using global phospho-proteome approaches, we observe acute activation of MAPK signaling by DUSP1/6 inhibition. This promotes accumulation of mitochondrial reactive oxygen species and, thereby, DNA damage and apoptotic cell death in CLL cells. Finally, we observe that DUSP1/6 inhibition is particularly effective against treatment-resistant CLL and therefore suggest transient DUSP1/6 inhibition as a promising treatment concept to eliminate drug-resistant CLL cells

Making sense of missense variants in TTN-related congenital myopathies.

Mutations in the sarcomeric protein titin, encoded by TTN, are emerging as a common cause of myopathies. The diagnosis of a TTN-related myopathy is, however, often not straightforward due to clinico-pathological overlap with other myopathies and the prevalence of TTN variants in control populations. Here, we present a combined clinico-pathological, genetic and biophysical approach to the diagnosis of TTN-related myopathies and the pathogenicity ascertainment of TTN missense variants. We identified 30 patients with a primary TTN-related congenital myopathy (CM) and two truncating variants, or one truncating and one missense TTN variant, or homozygous for one TTN missense variant. We found that TTN-related myopathies show considerable overlap with other myopathies but are strongly suggested by a combination of certain clinico-pathological features. Presentation was typically at birth with the clinical course characterized by variable progression of weakness, contractures, scoliosis and respiratory symptoms but sparing of extraocular muscles. Cardiac involvement depended on the variant position. Our biophysical analyses demonstrated that missense mutations associated with CMs are strongly destabilizing and exert their effect when expressed on a truncating background or in homozygosity. We hypothesise that destabilizing TTN missense mutations phenocopy truncating variants and are a key pathogenic feature of recessive titinopathies that might be amenable to therapeutic intervention

Mapping patterns of mineral alteration in volcanic terrains using ASTER data and field spectrometry in Southern Peru

Because formation of ore deposits is linked to volcanic and post-volcanic processes, an understanding of alteration style in volcanic regions has important applications in economic geology. We use ASTER (Advanced Spaceborne Thermal Emission and Reflection Radiometer) data and field spectrometry for mineral mapping in selected Miocene to Quaternary volcanic areas in Southern Peru to better characterize and understand the Tertiary volcanic evolution in this region. Our goal is to characterize volcanic regions near Puquio (Ayacucho) by correlating areas of intense alteration and related ignimbrite outflow sheets. In particular, we spectrally and mineralogically map different types and intensities of alteration based on remote sensing and ground-truth data. ASTER ratio images, alteration indices and false color composites were used to select ground-training areas for sample collection and field spectrometry. Alteration samples were characterized geochemically, mineralogically and spectrally. Absorption features correlate with chemical properties (e.g. iron content). Hyperspectral data from field spectrometry allow identification of important alteration minerals such as kaolinite and smectite. Alteration mineral assemblages range from silicic to argillic to “zeolite-type”. Using a support vector machine classification (SVM) algorithm on ASTER data, we mapped the different types and intensities of alteration, along with unaltered ignimbrite and lava flows with an accuracy of 80%. We propose a preliminary model for the interpretation of alteration settings, discuss the potential eruption sites of the ignimbrites in the region and, propose pH and temperature estimates for the respective classes based on the mineral assemblages identified