Computational Stem Cell Biology: Open Questions and Guiding Principles

Computational biology is enabling an explosive growth in our understanding of stem cells and our ability to use them for disease modeling, regenerative medicine, and drug discovery. We discuss four topics that exemplify applications of computation to stem cell biology: cell typing, lineage tracing, trajectory inference, and regulatory networks. We use these examples to articulate principles that have guided computational biology broadly and call for renewed attention to these principles as computation becomes increasingly important in stem cell biology. We also discuss important challenges for this field with the hope that it will inspire more to join this exciting area

Global analysis of the TRAPPIST Ultra-Cool Dwarf Transit Survey

ABSTRACT We conducted a global analysis of the TRAPPIST Ultra-Cool Dwarf Transit Survey – a prototype of the SPECULOOS transit search conducted with the TRAPPIST-South robotic telescope in Chile from 2011 to 2017 – to estimate the occurrence rate of close-in planets such as TRAPPIST-1b orbiting ultra-cool dwarfs. For this purpose, the photometric data of 40 nearby ultra-cool dwarfs were reanalysed in a self-consistent and fully automated manner starting from the raw images. The pipeline developed specifically for this task generates differential light curves, removes non-planetary photometric features and stellar variability, and searches for transits. It identifies the transits of TRAPPIST-1b and TRAPPIST-1c without any human intervention. To test the pipeline and the potential output of similar surveys, we injected planetary transits into the light curves on a star-by-star basis and tested whether the pipeline is able to detect them. The achieved photometric precision enables us to identify Earth-sized planets orbiting ultra-cool dwarfs as validated by the injection tests. Our planet-injection simulation further suggests a lower limit of 10 per cent on the occurrence rate of planets similar to TRAPPIST-1b with a radius between 1 and 1.3 R⊕ and the orbital period between 1.4 and 1.8 d.</jats:p

LBT transmission spectroscopy of HAT-P-12b: confirmation of a cloudy atmosphere with no significant alkali features

The hot sub-Saturn-mass exoplanet HAT-P-12b is an ideal target for transmission spectroscopy because of its inflated radius. We observed one transit of the planet with the multi-object double spectrograph (MODS) on the Large Binocular Telescope (LBT) with the binocular mode and obtained an atmosphere transmission spectrum with a wavelength coverage of $\sim$ 0.4 -- 0.9 $\mathrm{\mu}$m. The spectrum is relatively flat and does not show any significant sodium or potassium absorption features. Our result is consistent with the revised Hubble Space Telescope (HST) transmission spectrum of a previous work, except that the HST result indicates a tentative detection of potassium. The potassium discrepancy could be the result of statistical fluctuation of the HST dataset. We fit the planetary transmission spectrum with an extensive grid of cloudy models and confirm the presence of high-altitude clouds in the planetary atmosphere. The fit was performed on the combined LBT and HST spectrum, which has an overall wavelength range of 0.4 -- 1.6 $\mathrm{\mu}$m. The LBT/MODS spectrograph has unique advantages in transmission spectroscopy observations because it can cover a wide wavelength range with a single exposure and acquire two sets of independent spectra simultaneously.Comment: 14 pages, 12 figures. Accepted for publication in Astronomy & Astrophysic

Stronger diversity effects with increased environmental stress : a study of multitrophic interactions between oak, powdery mildew and ladybirds

Recent research has suggested that increasing neighbourhood tree species diversity may mitigate the impact of pests or pathogens by supporting the activities of their natural enemies and/or reducing the density of available hosts. In this study, we attempted to assess these mechanisms in a multitrophic study system of young oak (Quercus), oak powdery mildew (PM, caused by Erysiphe spp.) and a mycophagous ladybird (Psyllobora vigintiduo-punctata). We assessed ladybird mycophagy on oak PM in function of different neighbourhood tree species compositions. We also evaluated whether these species interactions were modulated by environmental conditions as suggested by the Stress Gradient Hypothesis. We adopted a complementary approach of a field experiment where we monitored oak saplings subjected to a reduced rainfall gradient in a young planted forest consisting of different tree species mixtures, as well as a lab experiment where we independently evaluated the effect of different watering treatments on PM infections and ladybird mycophagy. In the field experiment, we found effects of neighbourhood tree species richness on ladybird mycophagy becoming more positive as the target trees received less water. This effect was only found as weather conditions grew drier. In the lab experiment, we found a preference of ladybirds to graze on infected leaves from trees that received less water. We discuss potential mechanisms that might explain this preference, such as emissions of volatile leaf chemicals. Our results are in line with the expectations of the Natural Enemies Hypothesis and support the hypothesis that biodiversity effects become stronger with increased environmental stress

Asmparts: assembly of biological model parts

We propose a new computational tool to produce models of biological systems by assembling models from biological parts. Our software not only takes advantage of modularity, but it also enforces standardisation in part characterisation by considering a model of each part. We have used model parts in SBML to design transcriptional networks. Our software is open source, it works in linux and windows platforms, and it could be used to automatically produce models in a server. Our tool not only facilitates model design, but it will also help to promote the establishment of a registry of model parts

The discovery of ash dieback in the UK: the making of a focusing event

Why did the identification of ‘Ash Dieback’ (Chalara Fraxinea) in 2012 in the UK catch the national media, public and political zeitgeist, and lead to policy changes, in a way that no other contemporary tree pest or pathogen outbreak has?The identification of Ash Dieback in the UK is conceptualised as a successful ‘focusing event’ and the ways in which it was socially constructed by the media, stakeholders and the government are analysed. National newspaper coverage contributed to the way that the disease was understood and was significant in driving the political response. Ash Dieback’s focal power derived from the perceived scale and nature of its impact; the initial attribution of blame on government; the ‘war-like’ response from the government; and Ash’s status as a threatened ‘native’ tree. The Ash Dieback focusing event has increased the salience of plant health issues amongst policymakers, the public and conservation organisations in the UK

Modelos de endemicidad a lo largo de un gradiente altitudinal en Sierra Nevada (España) y Lefka Ori (Creta, Grecia)

Aim: High mountains in the Mediterranean region of Europe are particularly rich in endemic vascular plants. We aimed to compare the altitudinal patterns of vascular plant species richness and the proportion of endemic species in two Mediterranean region: Lefka Ori on the island of Crete (Greece) and Sierra Nevada on the Iberian peninsula. Location: Sierra Nevada, Granada (Spain); Lefka Ori, Crete (Greece). Methods: Data from standardised permanent plots settings on summit sites (comprising eight plot sectors, covering the upeermost 10 altitudinal metres) of different elevations were used (GLORIA Multi-Summit approach; www.gloria.ac.at). Species numbers, rates of endemic species, and soils temperature were compared by means of ANCOVA and linear regression. Results: The two regions, though climatically similar, showed strikingly different patterns: In Sierra Nevada, the proportion of endemic vascular plants (species restricted to Sierra Nevada) showed a stepwise increase from the lowest to the highest summit. In contrast, the proportion of endemic species restricted to Crete was not significantly different between the four summits in Lefka Ori. In both regions the observed trends were largely consistent with the altitudinal distribution of the endemic species obtained from standard floras. Main conclusions: The geographic positions of the two regions, i.e. island versus mainland and the higher elevation of Sierra Nevada are suggested to be the primary causes of the observed differences. The high degree of endemism in the cold environments of Mediterranean mountains’ upper bioclimatic zones indicates a pronounced vulnerability to the impacts of climate change. A continued and intensified species monitoring in the mountains around the Mediterranean basin, therefore, should be considered as a priority research task.Objetivo: Las zonas de alta montaña en la región mediterránea europea son particularmente ricas en plantas vasculares endémicas. Nuestro objetivo es comparar los modelos altitudinales para la riqueza de plantas vasculares y la proporción de endemismos en dos regiones mediterráneas: Lefka Ori en la isla de Creta (Grecia) y Sierra Nevada en la Península Ibérica. Localización: Sierra Nevada, Granada (España); Lefka Ori, Creta (Grecia). Método: Los datos proceden de un muestreo estandarizado en varias cimas situadas a diferentes altitudes (GLORIA Multi-Summit approach; www.gloria.ac.at). El número de especies, tasas de endemicidad, y temperatura del suelo se compararon por medio de ANCOVA y regresión lineal. Resultados: Las dos regiones objeto de análisis, aunque similares climáticamente, muestran patrones llamativamente diferentes: en Sierra Nevada, la proporción de plantas vasculares endémicas (especies restringidas a Sierra Nevada) muestra un incremento gradual desde la cima más baja a la más alta. En contraste, la proporción de endemismos restringidos a Creta no fue significativamente diferente entre las cuatro cimas de Lefka Ori. Las tendencias observadas en ambas regiones fueron en gran parte consistentes con la distribución de las especies endémicas obtenida de las floras para cada región. Conclusiones principales: La posición geográfica de ambas regiones, por ejemplo. isla frente a continente, y la mayor elevación de Sierra Nevada se sugieren como las principales causas de las diferencias observadas. El alto grado de endemicidad en los ambientes fríos de las zonas bioclimáticas superiores de las montañas mediterráneas evidencia una marcada vulnerabilidad a los impactos del cambio climático. Por lo tanto, el seguimiento continuado e intensivo de las especies de montaña alrededor de la cuenca mediterránea, debería considerarse como una tarea investigadora prioritaria.He set up of the permanent plots and data collection was supported by the FP-5 project GLORIA-Europe (2001-2003) No EVK2-2000-00056 of the European Commission

The effects of stand characteristics on the understory vegetation in Quercus petraea and Q. cerris dominated forests

The shelterwood system used in Hungary has many effects on the composition and structure of the herb layer. The aim of our study was to identify the main variables that affect the occurence of herbs and seedlings in Turkey oak-sessile oak (Quercus cerris and Q. petraea) stands. The study was carried out in the Bükk mountains, Hungary. 122 sampling plots were established in 50-150 year old oak forests, where we studied the species composition and structure of the understorey and overstorey. The occurence of herbs was affected by canopy closure, the heterogenity and patchiness of the stand, the slope and the east-west component of the aspect. The composition of saplings was significantly explained by the ratio of the two major oak species in the stand and the proximity of the adult plants. An important result for forest management was that sessile oaks were able to regenerate almost only where they were dominant in the overstorey