A regularized functional regression model enabling transcriptome-wide dosage-dependent association study of cancer drug response

Cancer treatments can be highly toxic and frequently only a subset of the patient population will benefit from a given treatment. Tumour genetic makeup plays an important role in cancer drug sensitivity. We suspect that gene expression markers could be used as a decision aid for treatment selection or dosage tuning. Using in vitro cancer cell line dose-response and gene expression data from the Genomics of Drug Sensitivity in Cancer (GDSC) project, we build a dose-varying regression model. Unlike existing approaches, this allows us to estimate dosage-dependent associations with gene expression. We include the transcriptomic profiles as dose-invariant covariates into the regression model and assume that their effect varies smoothly over the dosage levels. A two-stage variable selection algorithm (variable screening followed by penalized regression) is used to identify genetic factors that are associated with drug response over the varying dosages. We evaluate the effectiveness of our method using simulation studies focusing on the choice of tuning parameters and cross-validation for predictive accuracy assessment. We further apply the model to data from five BRAF targeted compounds applied to different cancer cell lines under different dosage levels. We highlight the dosage-dependent dynamics of the associations between the selected genes and drug response, and we perform pathway enrichment analysis to show that the selected genes play an important role in pathways related to tumorigenesis and DNA damage response

Solar UV irradiance in a changing climate: Trends in europe and the significance of spectral monitoring in Italy

Review of the existing bibliography shows that the direction and magnitude of the long-term trends of UV irradiance, and their main drivers, vary significantly throughout Europe. Analysis of total ozone and spectral UV data recorded at four European stations during 1996–2017 reveals that long-term changes in UV are mainly driven by changes in aerosols, cloudiness, and surface albedo, while changes in total ozone play a less significant role. The variability of UV irradiance is large throughout Italy due to the complex topography and large latitudinal extension of the country. Analysis of the spectral UV records of the urban site of Rome, and the alpine site of Aosta reveals that differences between the two sites follow the annual cycle of the differences in cloudiness and surface albedo. Comparisons between the noon UV index measured at the ground at the same stations and the corresponding estimates from the Deutscher Wetterdienst (DWD) forecast model and the ozone monitoring instrument (OMI)/Aura observations reveal differences of up to 6 units between individual measurements, which are likely due to the different spatial resolution of the different datasets, and average differences of 0.5–1 unit, possibly related to the use of climatological surface albedo and aerosol optical properties in the retrieval algorithms

Almost one year of TROPOMI/S5P total ozone column data: global ground-based validation

Póster presentado en: ATMOS 2018, celebrado en Salzburgo (Austria) del 26 al 29 de noviembre de 2018.In this work we present the validation results of almost one year of TROPOMI Near Real Time (NRTI) and OFFLine (OFFL) data against ground-based quality-assured Brewer and Dobson total ozone column (TOC) measurements deposited in the World Ozone and Ultraviolet Radiation Data Center (WOUDC). Additionally, comparisons to Brewer measurements from the European Brewer Network (EUBREWNET) and the Canadian Network are performed, as well as to twilight zenith-sky measurements obtained with ZSL-DOAS (Zenith Scattered Light Differential Optical Absorption Spectroscopy) instruments, that form part of the SAOZ network (Système d'Analyse par Observation Zénitale) of the Network for the Detection of Atmospheric Composition Change (NDACC). Through the comparison of the TROPOMI measurements to the total ozone ground-based measurements from stations that are distributed globally, as the background truth, the dependence of the new instrument on latitude, cloud properties, solar zenith and viewing angles, among others, is examined. Validation results show that the mean bias and the standard deviation of the percentage difference between TROPOMI and QA ground TOC meet the product requirements

Corrigendum to "Satellite observations and model simulations of tropospheric NO₂ columns over south-eastern Europe" published in Atmos. Chem. Phys., 9, 6119–6134, 2009

No abstract available

TROPOMI/S5P total ozone column data: global ground-based validation and consistency with other satellite missions

In this work, the TROPOMI near real time (NRTI) and offline (OFFL) total ozone column (TOC) products are presented and compared to daily ground-based quality-assured Brewer and Dobson TOC measurements deposited in the World Ozone and Ultraviolet Radiation Data Centre (WOUDC). Additional comparisons to individual Brewer measurements from the Canadian Brewer Network and the European Brewer Network (Eubrewnet) are performed. Furthermore, twilight zenith-sky measurements obtained with ZSL-DOAS (Zenith Scattered Light Differential Optical Absorption Spectroscopy) instruments, which form part of the SAOZ network (Système d'Analyse par Observation Zénitale), are used for the validation. The quality of the TROPOMI TOC data is evaluated in terms of the influence of location, solar zenith angle, viewing angle, season, effective temperature, surface albedo and clouds. For this purpose, globally distributed ground-based measurements have been utilized as the background truth. The overall statistical analysis of the global comparison shows that the mean bias and the mean standard deviation of the percentage difference between TROPOMI and ground-based TOC is within 0 –1.5 % and 2.5 %–4.5 %, respectively. The mean bias that results from the comparisons is well within the S5P product requirements, while the mean standard deviation is very close to those limits, especially considering that the statistics shown here originate both from the satellite and the ground-based measurements.This research has been supported by the European Space Agency “Preparation and Operations of the Mission Performance Centre (MPC) for the Copernicus Sentinel-5 Precursor Satellite” (contract no. 4000117151/16/1-LG)

Validation of the IASI FORLI/EUMETSAT ozone products using satellite (GOME-2), ground-based (Brewer–Dobson, SAOZ, FTIR) and ozonesonde measurements

This paper assesses the quality of IASI (Infrared Atmospheric Sounding Interferometer)/Metop-A (IASI-A) and IASI/Metop-B (IASI-B) ozone (O3) products (total and partial O3 columns) retrieved with the Fast Optimal Retrievals on Layers for IASI Ozone (FORLI-O3; v20151001) software for 9 years (2008–July 2017) through an extensive intercomparison and validation exercise using independent observations (satellite, ground-based and ozonesonde). Compared with the previous version of FORLI-O3 (v20140922), several improvements have been introduced in FORLI-O3 v20151001, including absorbance look-up tables recalculated to cover a larger spectral range, with additional numerical corrections. This leads to a change of  ∼ 4&thinsp;% in the total ozone column (TOC) product, which is mainly associated with a decrease in the retrieved O3 concentration in the middle stratosphere (above 30&thinsp;hPa/25&thinsp;km). IASI-A and IASI-B TOCs are consistent, with a global mean difference of less than 0.3&thinsp;% for both daytime and nighttime measurements; IASI-A is slightly higher than IASI-B. A global difference of less than 2.4&thinsp;% is found for the tropospheric (TROPO) O3 column product (IASI-A is lower than IASI-B), which is partly due to a temporary issue related to the IASI-A viewing angle in 2015. Our validation shows that IASI-A and IASI-B TOCs are consistent with GOME-2 (Global Ozone Monitoring Experiment-2), Dobson, Brewer, SAOZ (Système d'Analyse par Observation Zénithale) and FTIR (Fourier transform infrared) TOCs, with global mean differences in the range of 0.1&thinsp;%–2&thinsp;% depending on the instruments compared. The worst agreement with UV–vis retrieved TOC (satellite and ground) is found at the southern high latitudes. The IASI-A and ground-based TOC comparison for the period from 2008 to July 2017 shows the long-term stability of IASI-A, with insignificant or small negative drifts of 1&thinsp;%–3&thinsp;%&thinsp;decade−1. The comparison results of IASI-A and IASI-B against smoothed FTIR and ozonesonde partial O3 columns vary with altitude and latitude, with the maximum standard deviation being seen for the 300–150&thinsp;hPa column (20&thinsp;%–40&thinsp;%) due to strong ozone variability and large total retrievals errors. Compared with ozonesonde data, the IASI-A and IASI-B O3 TROPO column (defined as the column between the surface and 300&thinsp;hPa) is positively biased in the high latitudes (4&thinsp;%–5&thinsp;%) and negatively biased in the midlatitudes and tropics (11&thinsp;%–13&thinsp;% and 16&thinsp;%–19&thinsp;%, respectively). The IASI-A-to-ozonesonde TROPO comparison for the period from 2008 to 2016 shows a significant negative drift in the Northern Hemisphere of −8.6±3.4&thinsp;%&thinsp;decade−1, which is also found in the IASI-A-to-FTIR TROPO comparison. When considering the period from 2011 to 2016, the drift value for the TROPO column decreases and becomes statistically insignificant. The observed negative drifts of the IASI-A TROPO O3 product (8&thinsp;%–16&thinsp;%&thinsp;decade−1) over the 2008–2017 period might be taken into consideration when deriving trends from this product and this time period.</p

Quality assessment of the Ozone_cci Climate Research Data Package (release 2017) – Part 2: Ground-based validation of nadir ozone profile data products

Atmospheric ozone plays a key role in air quality and the radiation budget of the Earth, both directly and through its chemical influence on other trace gases. Assessments of the atmospheric ozone distribution and associated climate change therefore demand accurate vertically resolved ozone observations with both stratospheric and tropospheric sensitivity, on both global and regional scales, and both in the long term and at shorter timescales. Such observations have been acquired by two series of European nadir-viewing ozone profilers, namely the scattered-light UV–visible spectrometers of the GOME family, launched regularly since 1995 (GOME, SCIAMACHY, OMI, GOME-2A/B, TROPOMI, and the upcoming Sentinel-5 series), and the thermal infrared emission sounders of the IASI type, launched regularly since 2006 (IASI on Metop platforms and the upcoming IASI-NG on Metop-SG). In particular, several Level-2 retrieved, Level-3 monthly gridded, and Level-4 assimilated nadir ozone profile data products have been improved and harmonized in the context of the ozone project of the European Space Agency's Climate Change Initiative (ESA Ozone_cci). To verify their fitness for purpose, these ozone datasets must undergo a comprehensive quality assessment (QA), including (a) detailed identification of their geographical, vertical, and temporal domains of validity; (b) quantification of their potential bias, noise, and drift and their dependences on major influence quantities; and (c) assessment of the mutual consistency of data from different sounders. For this purpose we have applied to the Ozone_cci Climate Research Data Package (CRDP) released in 2017 the versatile QA and validation system Multi-TASTE, which has been developed in the context of several heritage projects (ESA's Multi-TASTE, EUMETSAT's O3M-SAF, and the European Commission's FP6 GEOmon and FP7 QA4ECV). This work, as the second in a series of four Ozone_cci validation papers, reports for the first time on data content studies, information content studies and ground-based validation for both the GOME- and IASI-type climate data records combined. The ground-based reference measurements have been provided by the Network for the Detection of Atmospheric Composition Change (NDACC), NASA's Southern Hemisphere Additional Ozonesonde programme (SHADOZ), and other ozonesonde and lidar stations contributing to the World Meteorological Organisation's Global Atmosphere Watch (WMO GAW). The nadir ozone profile CRDP quality assessment reveals that all nadir ozone profile products under study fulfil the GCOS user requirements in terms of observation frequency and horizontal and vertical resolution. Yet all L2 observations also show sensitivity outliers in the UTLS and are strongly correlated vertically due to substantial averaging kernel fluctuations that extend far beyond the kernel's 15 km FWHM. The CRDP typically does not comply with the GCOS user requirements in terms of total uncertainty and decadal drift, except for the UV–visible L4 dataset. The drift values of the L2 GOME and OMI, the L3 IASI, and the L4 assimilated products are found to be overall insignificant, however, and applying appropriate altitude-dependent bias and drift corrections make the data fit for climate and atmospheric composition monitoring and modelling purposes. Dependence of the Ozone_cci data quality on major influence quantities – resulting in data screening suggestions to users – and perspectives for the Copernicus Sentinel missions are additionally discussed

Venus' atmospheric water vapour in view of the arrival of the Venus Express mission.

International audienc