Max von Kleist

Max von Kleist
Robert Koch Institut | RKI · Bioinformatics (MF1)

PhD

About

141
Publications
10,596
Reads
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873
Citations
Additional affiliations
May 2019 - present
Robert Koch Institut
Position
  • Group Leader
October 2011 - April 2019
Freie Universität Berlin, Matheon
Position
  • Group Leader
January 2010 - October 2011
Freie Universität Berlin
Position
  • PostDoc Position

Publications

Publications (141)
Article
Background Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 and the resulting efforts to track the spread of this and other SARS-CoV-2 variants of concern led to an expansion of genomic sequencing activities in Germany. Method...
Article
Full-text available
RNA dimerization is the noncovalent association of two human immunodeficiency virus-1 (HIV-1) genomes. It is a conserved step in the HIV-1 life cycle and assumed to be a prerequisite for binding to the viral structural protein Pr55Gag during genome packaging. Here, we developed functional analysis of RNA structure-sequencing (FARS-seq) to comprehen...
Article
Full-text available
The role of schools as a source of infection and driver in the coronavirus-pandemic has been controversial and is still not completely clarified. To prevent harm and disadvantages for children and adolescents, but also adults, detailed data on school outbreaks is needed, especially when talking about open schools employing evidence-based safety con...
Article
Full-text available
Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the...
Article
Full-text available
Variability of synapse numbers and partners despite identical genes reveals the limits of genetic determinism. Here, we use developmental temperature as a non-genetic perturbation to study variability of brain wiring and behavior in Drosophila. Unexpectedly, slower development at lower temperatures increases axo-dendritic branching, synapse numbers...
Preprint
Full-text available
Modelling and simulating the dynamics of pathogen spreading has been proven crucial to inform public heath decisions, containment strategies, as well as cost-effectiveness calculations. Pathogen spreading is often modelled as a stochastic process that is driven by pathogen exposure on time-evolving contact networks. In adaptive networks , the sprea...
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By October 2021, 230 million SARS-CoV-2 diagnoses have been reported. Yet, a considerable proportion of cases remains undetected. Here, we propose GInPipe, a method that rapidly reconstructs SARS-CoV-2 incidence profiles solely from publicly available, time-stamped viral genomes. We validate GInPipe against simulated outbreaks and elaborate phylody...
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Single-cell RNA sequencing (scRNA-seq) has become ubiquitous in biology. Recently, there has been a push for using scRNA-seq snapshot data to infer the underlying gene regulatory networks (GRNs) steering cellular function. To date, this aspiration remains unrealized due to technical and computational challenges. In this work we focus on the latter,...
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Zusammenfassung Die weltweite Ausbreitung des Coronavirus SARS-CoV‑2 hat Gesundheits‑, Wirtschafts- und Gesellschaftssysteme massiv in Mitleidenschaft gezogen. Obwohl mittlerweile effektive Impfstoffe zur Verfügung stehen, ist es wahrscheinlich, dass der Erreger endemisch wird und uns noch über Jahre begleitet. Um andere und sich selbst möglichst e...
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Here, we report on the increasing frequency of the SARS-CoV-2 lineage A.27 in Germany during the first months of 2021. Genomic surveillance identified 710 A.27 genomes in Germany as of 2 May 2021, with a vast majority identified in laboratories from a single German state (Baden-Wuerttemberg, n = 572; 80.5%). Baden-Wuerttemberg is located near the b...
Preprint
Full-text available
Pre-exposure prophylaxis (PrEP) is an important pillar to prevent HIV transmission. Because of experimental and clinical shortcomings, mathematical models that integrate pharmacological, viral- and host factors are frequently used to quantify clinical efficacy of PrEP. Stochastic simulations of these models provides sample statistics from which the...
Article
Full-text available
The combination of the two nucleoside reverse transcriptase inhibitors (NRTI) tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is used in most highly active antiretroviral therapies for treatment of HIV-1 infection, as well as in pre-exposure prophylaxis against HIV acquisition. Administered as prodrugs, these drugs are taken up by HIV-i...
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Full-text available
Background During the initial COVID-19 response, Germany's Federal Government implemented several nonpharmaceutical interventions (NPIs) that were instrumental in suppressing early exponential spread of SARS-CoV-2. NPI effect on the transmission of other respiratory viruses has not been examined at the national level thus far. Methods Upper respir...
Preprint
Full-text available
Genome dimerization is a conserved feature of retroviral replication and a critical step in the HIV-1 life cycle, but how it is regulated is incompletely understood. Here, we developed FARS-seq (Functional Analysis of RNA Structure) to comprehensively identify sequences and structures within the HIV-1 5’UTR influencing dimerization. We found nucleo...
Preprint
Full-text available
By May 2021, over 160 million SARS-CoV-2 diagnoses have been reported worldwide. Yet, the true number of infections is unknown and believed to exceed the reported numbers by several fold. National testing policies, in particular, can strongly affect the proportion of undetected cases. Here, we propose a novel method (GInPipe) that reconstructs SARS...
Preprint
Full-text available
In May 2021, over 160 million SARS-CoV-2 infections have been reported worldwide. Yet, the true amount of infections is unknown and believed to exceed the reported numbers by several fold, depending on national testing policies that can strongly affect the proportion of undetected cases. To overcome this testing bias and better assess SARS-CoV-2 tr...
Preprint
Full-text available
Variability of synapse numbers and partners despite identical genes reveals limits of genetic determinism. Non-genetic perturbation of brain wiring can therefore reveal to what extent synapse formation is precise and absolute, or promiscuous and relative. Here, we show the role of relative partner availability for synapse formation in the fly brain...
Preprint
Single cell RNA-sequencing (scRNA-seq) has become ubiquitous in biology. Recently, there has been a push for using scRNA-seq snapshot data to infer the underlying gene regulatory networks (GRNs) steering cellular function. To date, this aspiration remains unrealised due to technical- and computational challenges. In this work, we focus on the latte...
Article
Full-text available
The SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in acute or convalescent CO...
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Many recent studies highlight the fundamental importance of viruses. Besides their important role as human and animal pathogens, their beneficial, commensal or harmful functions are poorly understood. By developing and applying tailored bioinformatical tools in important virological models, the Marie Skłodowska-Curie Initiative International Traini...
Article
Deep convolutional neural networks (DCNNs) are routinely used for image segmentation of biomedical data sets to obtain quantitative measurements of cellular structures like tissues. These cellular structures often contain gaps in their boundaries, leading to poor segmentation performance when using DCNNs like the U-Net. The gaps can usually be corr...
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Non-pharmaceutical interventions (NPIs) remain decisive tools to contain SARS-CoV-2. Strategies that combine NPIs with testing may improve efficacy and shorten quarantine durations. We develop a stochastic within-host model of SARS-CoV-2 that captures temporal changes in test sensitivities, incubation- and infectious periods. We use the model to si...
Article
Full-text available
While large-scale vaccination campaigns against SARS-CoV-2 are rolled out at the time of writing, non-pharmaceutical interventions (NPIs), including the isolation of infected individuals, and quarantine of exposed individuals remain central measures to contain the spread of SARS-CoV-2. Strategies that combine NPIs with innovative SARS-CoV-2 testing...
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Full-text available
Zusammenfassung Beim ersten Auftreten des Erregers SARS-CoV‑2 im Dezember 2019 standen weder spezifische therapeutische Möglichkeiten noch ein Impfstoff zur Verfügung. Auch in Deutschland rückten deshalb nichtpharmakologische Maßnahmen zur Kontrolle der COVID-19-Pandemie in den Vordergrund. Am Robert Koch-Institut wurde eine Multikomponentenstrateg...
Article
Das Betacoronavirus SARS-CoV-2 gelangte höchstwahrscheinlich als zoonotischer Erreger gegen Ende 2019 in die menschliche Bevölkerung, vermutlich in Form einer einzelnen Transmission (monophyletischer Ursprung) aus einem noch immer unbekannten Tierreservoir (1, 2). Ebenso wie zum Beispiel bei Influenzaviren und HIV handelt es sich bei SARS-CoV-2 um...
Preprint
Full-text available
While large-scale vaccination campaigns against SARS-CoV-2 are rolled out at the time of writing, non-pharmaceutical interventions (NPIs), including the isolation of infected individuals, and quarantine of exposed individuals remain central measures to contain the spread of SARS-CoV-2. Strategies that combine NPIs with innovative SARS-CoV-2 testing...
Article
Full-text available
Schnelltests ergeben nur dann Sinn, wenn Gruppen getestet werden, die einen hohen Anteil an Infizierten aufweisen - andernfalls erhält man zu viele falsch positive Ergebnisse. Das Robert Koch-Institut hat eine Infografik erstellt, die das Problem unterschiedlicher Testansätze aufzeigt.
Article
Full-text available
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need...
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Full-text available
In 2017-2018, a fipronil contamination occurred in the European chicken egg supply chain due to its illegal use as insecticide to control red lice infestations. Fipronil has the potential to be transferred into eggs of laying hens, thereby entering the food chain. Here, we present a toxicokinetic model to predict the transfer of fipronil in laying...
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Full-text available
In many bacteria the biofilm-promoting second messenger c-di-GMP is produced and degraded by multiple diguanylate cyclases (DGC) and phosphodiesterases (PDE), respectively. High target specificity of some of these enzymes has led to theoretical concepts of 'local' c-di-GMP signaling. In Escherichia coli K-12, which has 12 DGCs and 13 PDEs, a single...
Preprint
Full-text available
SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need...
Article
Full-text available
Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partners when given the opportunity. Dynamic axon-dendritic positioning can restrict synaptogenic encounters, but the spatiotemporal interaction kinetics and their regulation remain essentially unknown inside developing brains. Here we show that the kinetics o...
Preprint
Full-text available
Brain wiring is remarkably precise, yet most neurons readily form synapses with incorrect partners when given the opportunity. Dynamic axon-dendritic positioning can restrict synaptogenic encounters, but the spatiotemporal interaction kinetics and their regulation remain essentially unknown inside developing brains. Here we show that the kinetics o...
Article
Graphical Abstract Highlights d Stochastic filopodia dynamics are required for robust synapse formation in fly brains d Only 1-2 filopodia at a time contain synaptic seeding factors and are synaptogenic d 4D tracking and computational modeling support a serial synapse formation model d Synapse formation prevents axonal retraction Correspondence rob...
Article
Muscle fibre cross-sectional area (CSA) is an important biomedical measure used to determine the structural composition of skeletal muscle, and it is relevant for tackling research questions in many different fields of research. To date, time consuming and tedious manual delineation of muscle fibres is often used to determine the CSA. Few methods a...
Article
Full-text available
Osteoarthritis (OA) is the most common cause of disability in ageing societies, with no effective therapies available to date. Two preclinical models are widely used to validate novel OA interventions (MCL-MM and DMM). Our aim is to discern disease dynamics in these models to provide a clear timeline in which various pathological changes occur. OA...
Data
Change point analysis, sample size selection, zoning, thresholding and contouring, classification. (PDF)
Data
Immunofluorescent staining of collagen type II (red), viable (DAPI, blue) and apoptotic chondrocytes (TUNEL, green) in frontal mouse knee sections at different time points. On the basis of these sections the computer assisted detection of chondrocytes and apoptotic chondrocytes was done (see Fig 5). (TIF)
Data
Comparison of proteoglycan loss and lesion formation in the MCL-MM (A) and DMM (B) model. (TIF)
Data
Immunofluorescent staining of collagen degradation products (green) and cell nuclei (blue) in sham mice. Images show a frontal view on the lateral and medial aspect of the knee joint. FC-femoral condyle; TP-tibial plateau; Bar = 250μm. (TIF)
Article
HIV-1 subtype A is the second most prevalent subtype worldwide, with a high prevalence in Eastern Africa and Eastern Europe. However, an increase of non-B infections, including subtype A infections, has been observed in Germany and other European countries. There has simultaneously been an increased flow of refugees into Europe and especially into...
Article
Full-text available
Pre-exposure prophylaxis (PrEP) is considered one of the five “pillars” by UNAIDS to reduce HIV transmission. Moreover, it is a tool for female self-protection against HIV, making it highly relevant to sub-Saharan regions, where women have the highest infection burden. To date, Truvada is the only medication for PrEP. However, the cost of Truvada l...
Data
This supplementary text quantifies the probability of EFV resistance emergence prior to PEP initiation. We derive the probability of resistance emergence as a function of the time between virus exposure and start of post-exposure prophylaxis. The aim is to provide decision support on whether to start PEP after suspected exposure or not.
Data
The table shows the individual pharmacokinetic parameters (CLss/Fbio, V/Fbio and ka) of all virtual patients.
Data
The table shows the considered single nucleotide polymorphisms associated with EFV metabolism and how they were modeled to affect efavirenz apparent oral clearance in the population pharmacokinetic model.
Data
The figure shows an example of a concentration-time profile for chronic PrEP with 400 mg oral EFV and 25% adherence, where a temporal window for infection arises and EFV concentrations are insufficient for protection.
Data
The supplementary text contains an in-depth analysis of EFV cellular uptake, providing support for the free drug hypothesis and for equilibrative transport or passive diffusion as the main cellular uptake mechanisms of EFV. Furthermore, it analyses whether the drug potency is sensitive to uncertainty in drug binding.
Article
Full-text available
Paratuberculosis is a major disease in cattle that severely affects animal welfare and causes huge economic losses worldwide. Development of alternative diagnostic methods is of urgent need to control the disease. Recent studies suggest that long non-coding RNAs (lncRNAs) play a crucial role in regulating immune function and may confer valuable inf...
Article
Full-text available
Currently, there is no effective vaccine to halt HIV transmission. However, pre-exposure prophylaxis (PrEP) with the drug combination Truvada can substantially decrease HIV transmission in individuals at risk. Despite its benefits, Truvada-based PrEP is expensive and needs to be taken once-daily, which often leads to inadequate adherence and incomp...
Data
The Supplementary Text contains a step-by-step derivation of the equations for the extinction/infection probability presented in the main article. (PDF)
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The Supplementary Text contains a sensitivity analysis with respect to viral dynamics parameters. (PDF)
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The Supplementary Text compares the EC50 and EC90 (antiviral concentrations that provide 50- and 90% protection) after viral challenge with (i) a single virus V^, and after virus challenges (ii) sampled from the distribution for homosexual exposure, Eq (24). (PDF)
Data
The Supplementary Text contains details of the protein-binding adjustment for pharmacodynamic parameters. (PDF)
Data
The Supplementary Text contains details of the IC50-to-EC50 conversion. (PDF)
Preprint
Following axon pathfinding, growth cones transition from stochastic filopodial exploration to the formation of a limited number of synapses. How the interplay of filopodia and synapse assembly ensures robust connectivity in the brain has remained a challenging problem. Here, we developed a new 4D analysis method for filopodial dynamics and a data-d...
Article
Full-text available
To achieve the 90-90-90 goals set by UNAIDS, the number of new HIV infections needs to decrease to approximately 500,000 by 2020. One of the ‘five pillars’ to achieve this goal is pre-exposure prophylaxis (PrEP). Truvada (emtricitabine-tenofovir) is currently the only medication approved for PrEP. Despite its advantages, Truvada is costly and requi...
Data