| 1. |
- Bailey, Matthew H., et al.
(author)
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Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
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| 2. |
- Campbell, PJ, et al.
(author)
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Pan-cancer analysis of whole genomes
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Journal article (peer-reviewed)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 3. |
- Chu, Matthew R., et al.
(author)
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An imaging polarimetry survey of Type Ia supernovae : are peculiar extinction and polarization properties produced by circumstellar or interstellar matter?
- 2022
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 509:4, s. 6028-6046
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Journal article (peer-reviewed)abstract
- Some highly reddened Type Ia supernovae (SNe Ia) display low total-to-selective extinction ratios (RV ≲ 2) in comparison to that of typical Milky Way dust (RV ≈ 3.3), and polarization curves that rise steeply to blue wavelengths, with peak polarization values at short wavelengths (λmax<0.4μ) in comparison to the typical Galactic values (λmax≈0.55μ m). Understanding the source of these properties could provide insight into the progenitor systems of SNe Ia. We aim to determine whether they are the result of the host galaxy’s interstellar dust or circumstellar dust. This is accomplished by analysing the continuum polarization of 66 SNe Ia in dust-rich spiral galaxies and 13 SNe Ia in dust-poor elliptical galaxies as a function of normalized galactocentric distance. We find that there is a general trend of SNe Ia in spiral galaxies displaying increased polarization values when located closer to the host galaxies’ centre, while SNe Ia in elliptical host galaxies display low polarization. Furthermore, all highly polarized SNe Ia in spiral host galaxies display polarization curves rising toward blue wavelengths, while no evidence of such polarization properties is shown in elliptical host galaxies. This indicates that the source of the peculiar polarization curves is likely the result of interstellar material as opposed to circumstellar material. The peculiar polarization and extinction properties observed toward some SNe Ia may be explained by the radiative torque disruption mechanism induced by the SN or the interstellar radiation field.
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| 4. |
- Goobar, Ariel, 1962-, et al.
(author)
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Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky
- 2023
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In: Nature Astronomy. - 2397-3366. ; 7:9, s. 1098-1107
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Journal article (peer-reviewed)abstract
- Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.
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| 5. |
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| 6. |
- Karlsson, Linn, et al.
(author)
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Physical and Chemical Properties of Cloud Droplet Residuals and Aerosol Particles During the Arctic Ocean 2018 Expedition
- 2022
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In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 127:11
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Journal article (peer-reviewed)abstract
- Detailed knowledge of the physical and chemical properties and sources of particles that form clouds is especially important in pristine areas like the Arctic, where particle concentrations are often low and observations are sparse. Here, we present in situ cloud and aerosol measurements from the central Arctic Ocean in August–September 2018 combined with air parcel source analysis. We provide direct experimental evidence that Aitken mode particles (particles with diameters ≲70 nm) significantly contribute to cloud condensation nuclei (CCN) or cloud droplet residuals, especially after the freeze-up of the sea ice in the transition toward fall. These Aitken mode particles were associated with air that spent more time over the pack ice, while size distributions dominated by accumulation mode particles (particles with diameters ≳70 nm) showed a stronger contribution of oceanic air and slightly different source regions. This was accompanied by changes in the average chemical composition of the accumulation mode aerosol with an increased relative contribution of organic material toward fall. Addition of aerosol mass due to aqueous-phase chemistry during in-cloud processing was probably small over the pack ice given the fact that we observed very similar particle size distributions in both the whole-air and cloud droplet residual data. These aerosol–cloud interaction observations provide valuable insight into the origin and physical and chemical properties of CCN over the pristine central Arctic Ocean.
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| 7. |
- Kurganskiy, Alexander, et al.
(author)
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Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe
- 2021
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:13
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Journal article (peer-reviewed)abstract
- Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season.
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| 8. |
- Maitre, Léa, et al.
(author)
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State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event
- 2022
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In: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 168
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Journal article (peer-reviewed)abstract
- The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P > 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field.
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| 9. |
- Patti, Alessandro, et al.
(author)
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Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise
- 2023
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In: Clinics. - : ELSEVIER ESPANA. - 1807-5932 .- 1980-5322. ; 78
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Journal article (peer-reviewed)abstract
- Background: Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF.Methods: Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2.Results: Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 & PLUSMN; 3.8 vs. 32.5 & PLUSMN; 9.8 mL/Kg*min-1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 & PLUSMN; 9.8% for patients with CHF compared to 61.1 & PLUSMN; 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 & PLUSMN; 51.0, 132.0 & PLUSMN; 38.8 and 155.6 & PLUSMN; 45.5s) than in controls (58.08 & PLUSMN; 13.2, 74.3 & PLUSMN; 21.1, 96.7 & PLUSMN; 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 & PLUSMN; 3.3, 41.9 & PLUSMN; 29.1 and 25.0 & PLUSMN; 13.6%) than in controls (10.1 & PLUSMN; 4.6, 62.1 & PLUSMN; 17.7 and 38.7 & PLUSMN; 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF.Conclusions: Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.
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| 10. |
- Reyna, Matthew A, et al.
(author)
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Pathway and network analysis of more than 2500 whole cancer genomes
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
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Journal article (peer-reviewed)abstract
- The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
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| 11. |
- Rowney, Francis M, et al.
(author)
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Environmental DNA reveals links between abundance and composition of airborne grass pollen and respiratory health
- 2021
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In: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 31:9, s. 4-2003
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Journal article (peer-reviewed)abstract
- Grass (Poaceae) pollen is the most important outdoor aeroallergen,1 exacerbating a range of respiratory conditions, including allergic asthma and rhinitis ("hay fever").2-5 Understanding the relationships between respiratory diseases and airborne grass pollen with a view to improving forecasting has broad public health and socioeconomic relevance. It is estimated that there are over 400 million people with allergic rhinitis6 and over 300 million with asthma, globally,7 often comorbidly.8 In the UK, allergic asthma has an annual cost of around US$ 2.8 billion (2017).9 The relative contributions of the >11,000 (worldwide) grass species (C. Osborne et al., 2011, Botany Conference, abstract) to respiratory health have been unresolved,10 as grass pollen cannot be readily discriminated using standard microscopy.11 Instead, here we used novel environmental DNA (eDNA) sampling and qPCR12-15 to measure the relative abundances of airborne pollen from common grass species during two grass pollen seasons (2016 and 2017) across the UK. We quantitatively demonstrate discrete spatiotemporal patterns in airborne grass pollen assemblages. Using a series of generalized additive models (GAMs), we explore the relationship between the incidences of airborne pollen and severe asthma exacerbations (sub-weekly) and prescribing rates of drugs for respiratory allergies (monthly). Our results indicate that a subset of grass species may have disproportionate influence on these population-scale respiratory health responses during peak grass pollen concentrations. The work demonstrates the need for sensitive and detailed biomonitoring of harmful aeroallergens in order to investigate and mitigate their impacts on human health.
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