Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives

A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease

A Universal Power-law Prescription for Variability from Synthetic Images of Black Hole Accretion Flows

We present a framework for characterizing the spatiotemporal power spectrum of the variability expected from the horizon-scale emission structure around supermassive black holes, and we apply this framework to a library of general relativistic magnetohydrodynamic (GRMHD) simulations and associated general relativistic ray-traced images relevant for Event Horizon Telescope (EHT) observations of Sgr A*. We find that the variability power spectrum is generically a red-noise process in both the temporal and spatial dimensions, with the peak in power occurring on the longest timescales and largest spatial scales. When both the time-averaged source structure and the spatially integrated light-curve variability are removed, the residual power spectrum exhibits a universal broken power-law behavior. On small spatial frequencies, the residual power spectrum rises as the square of the spatial frequency and is proportional to the variance in the centroid of emission. Beyond some peak in variability power, the residual power spectrum falls as that of the time-averaged source structure, which is similar across simulations; this behavior can be naturally explained if the variability arises from a multiplicative random field that has a steeper high-frequency power-law index than that of the time-averaged source structure. We briefly explore the ability of power spectral variability studies to constrain physical parameters relevant for the GRMHD simulations, which can be scaled to provide predictions for black holes in a range of systems in the optically thin regime. We present specific expectations for the behavior of the M87* and Sgr A* accretion flows as observed by the EHT

Prevalence and correlates of self-harm in the German general population

The study aimed at evaluating the psychometric properties of the German version of the Self- Harm Inventory (SHI) and examining the lifetime prevalence and correlates of self-harm in a representative German population sample (N = 2,507; age mean = 48.79, SD = 18.11; range 14 to 94 years; 55.5% women) using the SHI. All participants answered the German SHI, the short form of the Barratt Impulsiveness Scale (BIS-15), the ultra-brief Patient Health Questionnaire for Depression and Anxiety (PHQ-4), and provided sociodemographic information. The one-factorial structure of the SHI was replicated using a confirmatory factor analysis. Internal consistency coefficients were sufficient and in line with previous studies. Almost half of the sample (49%) acknowledged at least one self-harming behavior over the life-span, most frequently indirect forms of self-harm. The rate of participants who engaged in at least one SHI behavior was higher among men than women (51.6% vs. 46.9%, respectively, χ2 = 5.38, p = 0.020). Higher SHI scores were related to younger age, male gender, living alone, more symptoms of anxiety and depression (PHQ-4), higher impulsivity scores (BIS-15), and suffering from obesity grade 2. Women engaged more often in discreet forms of self-harm than men, e.g., preventing wounds from healing, exercising an injury, starving, and abusing laxatives. In terms of other indirect self-harming behaviors, men admitted more often driving recklessly, being promiscuous and losing a job on purpose, while women reported more frequently engaging in emotionally abusive relationships. With respect to direct self-harm, women were more likely to endorse suicide attempts and cutting, while men admitted more often head-banging. The findings suggest that self-harm constitutes a common problem. Future longitudinal studies are required to examine the natural course, sociodemographic and psychopathological risk factors, as well as possible time-trends of self-harming behaviors in more depth