Modelling a high-mass red giant observed by CoRoT

The G6 giant HR\,2582 (HD\,50890) was observed by CoRoT for approximately 55 days. Mode frequencies are extracted from the observed Fourier spectrum of the light curve. Numerical stellar models are then computed to determine the characteristics of the star (mass, age, etc...) from the comparison with observational constraints. We provide evidence for the presence of solar-like oscillations at low frequency, between 10 and 20\,$\mu$Hz, with a regular spacing of $(1.7\pm0.1)\mu$Hz between consecutive radial orders. Only radial modes are clearly visible. From the models compatible with the observational constraints used here, We find that HR\,2582 (HD\,50890) is a massive star with a mass in the range (3--\,5\,$M_{\odot}$), clearly above the red clump. It oscillates with rather low radial order ($n$ = 5\,--\,12) modes. Its evolutionary stage cannot be determined with precision: the star could be on the ascending red giant branch (hydrogen shell burning) with an age of approximately 155 Myr or in a later phase (helium burning). In order to obtain a reasonable helium amount, the metallicity of the star must be quite subsolar. Our best models are obtained with a mixing length significantly smaller than that obtained for the Sun with the same physical description (except overshoot). The amount of core overshoot during the main-sequence phase is found to be mild, of the order of 0.1\,$H_{\rm p}$.Comment: Accepted in A&

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1–2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)—that could be quantified in semen for paternal cases (recurrence risks of 5.6–12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1-2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)-that could be quantified in semen for paternal cases (recurrence risks of 5.6-12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling

Stellar Structure and Evolution: Deductions from Hipparcos

During the last decade, the understanding of fine features of the structure and evolution of stars has become possible as a result of enormous progress made in the acquisition of high-quality observational and experimental data and of new developments and refinements in the theoretical description of stellar plasmas. The confrontation of high-quality observations with sophisticated stellar models has allowed many aspects of the theory to be validated, and several characteristics of stars relevant to Galactic evolution and cosmology to be inferred. This paper is a review of the results of recent studies undertaken in the context of the Hipparcos mission, taking benefit of the high-quality astrometric data it has provided. Successes are discussed, as well as the problems that have arisen and suggestions proposed to solve them. Future observational and theoretical developments expected and required in the field are also presented.Comment: 56 pages, including 9 figures, Ann. Rev. Astron. Astrophys. Vol. 38, September 2000 (in press

Multimodal analysis of cell-free DNA whole-genome sequencing for pediatric cancers with low mutational burden

Sequencing of cell-free DNA in the blood of cancer patients (liquid biopsy) provides attractive opportunities for early diagnosis, assessment of treatment response, and minimally invasive disease monitoring. To unlock liquid biopsy analysis for pediatric tumors with few genetic aberrations, we introduce an integrated genetic/epigenetic analysis method and demonstrate its utility on 241 deep whole-genome sequencing profiles of 95 patients with Ewing sarcoma and 31 patients with other pediatric sarcomas. Our method achieves sensitive detection and classification of circulating tumor DNA in peripheral blood independent of any genetic alterations. Moreover, we benchmark different metrics for cell-free DNA fragmentation analysis, and we introduce the LIQUORICE algorithm for detecting circulating tumor DNA based on cancer-specific chromatin signatures. Finally, we combine several fragmentation-based metrics into an integrated machine learning classifier for liquid biopsy analysis that exploits widespread epigenetic deregulation and is tailored to cancers with low mutation rates. Clinical associations highlight the potential value of cfDNA fragmentation patterns as prognostic biomarkers in Ewing sarcoma. In summary, our study provides a comprehensive analysis of circulating tumor DNA beyond recurrent genetic aberrations, and it renders the benefits of liquid biopsy more readily accessible for childhood cancers