SARS-CoV-2 Through the Lens of Computational Biology:How bioinformatics is playing a key role in the study of the virus and its origins

In December 2019, the Chinese Center for Disease Control reported several cases of severe pneumonia that resisted usual treatments inthe city of Wuhan. This announcement marked the beginning of the COVID19 pandemic, which caused more than 80 million infection casesand 1.7 million deaths worldwide in 2020 alone and is still raging. The pandemic has given rise to global public health responses and international research efforts of unprecedented scope and speed. This scientific mobilization has yielded remarkable results, enabling a great deal of knowledge accumulation in just a few months: from the identification of the virus and its main proteins to the analysis of its origin and mechanisms. This basic biological knowledge is mandatory for medical advances.In this document, one year after the beginning of the spread of the disease, we wish to shed particular light on the contribution of bioinformatics in all this work. This discipline, at the crossroads of computer sciences, mathematics, biology, and physics, has taken oninestimable importance in modern biology and medicine. It provides computational models, algorithms, software, and guidelines to help thescientific community handle biological data and accelerate research. The discovery and study of the SARS-CoV-2 coronavirus is an emblematicexample of these contributions. Bioinformatics methods have been at the heart of several essential milestones: sequencing the virus genome, analyzing its origin and evolutionary dynamics, modeling interacting biological entities at the structural and network scales, and studying host genetic susceptibility. For several of these topics, research on SARS-CoV-2 could benefit from a wide range of off-the-shelf software packages that rely on well-established algorithms developed by the bioinformatics community over the years. For other topics, the analysis of SARS-CoV-2 pushes the limits of knowledge and invites the community to develop new computational models and methods. This work, as a whole, has made it possible to elucidate the nature and the functioning of the novel pathogen. It has contributed to the fight against COVID19, even if much remains to be done to fully understand the disease and control the epidemic

Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection

International audienceHuman papillomaviruses (HPVs) are oncogenic viruses causing most cervical cancers. Highly prevalent in young, sexually active women, only a minority of HPV infections persist. To better characterize the immuno-modulatory impact of early HPV infections, we measured changes in a panel of 20 cytokines in cervicovaginal samples collected from young women who were tested for HPV and self-reported for genital inflammation and infection symptoms. Multi-factor statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection, and that macrophage inflammatory proteins were associated in particular with high-risk HPV infections

Cumulative association of obstructive sleep apnea severity and short sleep duration with the risk for hypertension.

Obstructive sleep apnea (OSA) and short sleep duration are individually associated with an increased risk for hypertension (HTN). The aim of this multicenter cross-sectional study was to test the hypothesis of a cumulative association of OSA severity and short sleep duration with the risk for prevalent HTN. Among 1,499 patients undergoing polysomnography for suspected OSA, 410 (27.3%) previously diagnosed as hypertensive and taking antihypertensive medication were considered as having HTN. Patients with total sleep time (TST) <6 h were considered to be short sleepers. Logistic regression procedures were performed to determine the independent association of HTN with OSA and sleep duration. Considering normal sleepers (TST ≥6 h) without OSA as the reference group, the odds ratio (OR) (95% confidence intervals) for having HTN was 2.51 (1.35-4.68) in normal sleepers with OSA and 4.37 (2.18-8.78) in short sleepers with OSA after adjustment for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, daytime sleepiness, poor sleep complaint, time in bed, sleep architecture and fragmentation, and study site. The risk for HTN appeared to present a cumulative association with OSA severity and short sleep duration (p<0.0001 for linear trend). The higher risk for HTN was observed in short sleepers with severe OSA (AHI ≥30) (OR, 4.29 [2.03-9.07]). In patients investigated for suspected OSA, sleep-disordered breathing severity and short sleep duration have a cumulative association with the risk for prevalent HTN. Further studies are required to determine whether interventions to optimize sleep may contribute to lower BP in patients with OSA

HPV cervical infections and serological status in vaccinated and unvaccinated women

International audienceUnderstanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. We investigate HPV prevalence and antibody status in 150 women (ages 18 to 25) in Montpellier, France. At inclusion and one month later, cervical swabs, blood samples and questionnaires (for demographics and behavioural variables) were collected. Oncogenic, non-vaccine genotypes HPV51, HPV66, HPV53, and HPV52 were the most frequently detected viral genotypes overall. Vaccination status, which was well-balanced in the cohort, showed the strongest (protective) eect against HPV infections, with an associated odds ratio for alphapapillo-mavirus detection of 0.45 (95% condence interval: [0.22;0.58]). We also identied signicant eects of age, number of partners, body mass index, and contraception status on HPV detection and on coinfec-tions. Type-specic IgG serological status was also largely explained by the vaccination status. IgM seropositivity was best explained by HPV detection at inclusion only. Finally, we identify a strong signicant eect of vaccination on genotype prevalence, with a striking under-representation of HPV51 in vaccinated women. Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective eect of the vaccine against HPV51 merits further investigation

Obstructive sleep apnea, chronic obstructive pulmonary disease and NAFLD: an individual participant data meta-analysis

International audienc

Multivariate adjusted Odds Ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep duration in the whole obstructive sleep apnea (OSA) group and in the 2 categories of OSA severity.

<p>SDB, sleep-disordered breathing.</p><p>OR were adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, time in bed, and study site.</p><p>* p<0.05.</p><p>**p<0.01.</p><p>Multivariate adjusted Odds Ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep duration in the whole obstructive sleep apnea (OSA) group and in the 2 categories of OSA severity.</p

Multivariate adjusted odds ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep-disordered breathing or sleep duration.

<p>OSA, obstructive sleep apnea.</p><p>Model 1 included OSA severity or sleep duration adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, time in bed, and study site.</p><p>Model 2 included OSA severity or sleep duration adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, sleep latency, and study site.</p><p>Model 3 included OSA severity or sleep duration adjusted for age, gender, obesity, diabetes, depression, current smoking, use of thyroid hormones, excessive daytime sleepiness, poor sleep, time spent in slow wave sleep, overall arousal index, wake time after sleep onset, and study site.</p><p>Adjusted OR were all statistically significant with p value <0.01</p>†<p>Tested by the Cochrane-Armitage trend test.</p><p>Multivariate adjusted odds ratio (OR) (95% confidence interval [CI]) for hypertension associated with sleep-disordered breathing or sleep duration.</p

Concomitant and productive genital infections by HSV-2 and HPV in two young women: a case report

Human papillomaviruses (HPVs), the most oncogenic virus known to humans, are often associated with Herpes Simplex Virus-2 (HSV-2) infections. The involvement of the latter in cervical cancer is controversial but its long-term infections might modulate the mucosal microenvironment in a way that favors carcinogenesis. We know little about coinfections between HSV-2 and HPVs, and studying the immunological and microbiological dynamics in the early stages of these infections may help identify or rule out potential interactions. We report two cases of concomitant productive, although asymptomatic, HSV-2 and HPV infections in young women (aged 20 and 25). The women were followed up for approximately a year, with clinical visits every two months and weekly self-samples. We performed quantitative analyses of their HSV-2 and HPV viral loads, immunological responses (IgG and IgM antibodies and local cytokines expression profiles), vaginal microbiota composition, as well as demographic and behavior data. We detect interactions between virus loads, immune response, and the vaginal microbiota, which improve our understanding of HSV-2 and HPVs' coinfections and calls for further investigation with larger cohorts

Characteristics of the study population.

<p>Data are expressed as mean (SD) or percentages.</p><p>HTN, hypertension; BMI, body mass index; EDS, excessive daytime sleepiness; WASO, wake time after sleep onset; REM, rapid eye movement; SW, slow wave.</p><p>Characteristics of the study population.</p