Epigenetic profiling of aging mouse brain at base resolution

Recent studies have proven that epigenetics, especially 5-methylcytosine (5mC), plays a pivotal role in aging. Along these lines, previous studies have reported diverse epigenetic profiles among different cell-types like neurons and oligodendrocytes of the same individual. Besides methylation, DNA undergoes various other types of epigenetic modification. It remains to be investigated if these modifications changes upon aging and can thus also serve as an alternative reliable molecular marker of the epigenetic age of an individual. Thus, it is essential to identify variations in other epigenetic modifications of DNA in specific cell-types from the same individual. We plan to study various modifications in a single chain reaction using long-read sequencing on the MinIon platform from ONT.

People involved: Dr. Akash Srivastava


Detecting RNA modifications with nanopore sequencing

RNA modifications such as the highly abundant N6-methyladenosine (m6A) are known as an important aspect of RNA biology. For example, m6A modification has been shown to be involved in the regulation of mRNA processing, but also RNA virus replication and translation. Second-generation sequencing methods for m6A detection are limited to position-only inference on known reference sequences. Nanopore direct RNA sequencing enables assessment of modification status of individual reads at single-nucleotide resolution, but current detection models are still limited to position-only inference. We aim to use deep neural networks for de-novo modification detection on nanopore data that achieves high accuracy at single read, single nucleotide resolution.

People involved: Sebastian Krautwurst

Related publications:

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Molecular serology for rapid determination of vaccination titers

The Permanent Vaccination Commission (STIKO) annually publishes a list of recommended vaccinations. A high vaccination rate in a population is the best requirement to prevent the spread of vaccine-preventable diseases. However, the present system is being challenged by massive migration of people from crisis areas. Therefore, we want to develop a novel diagnostic tool to determine, in a single test run, the antibody status against all vaccinations recommended by the STIKO. For this purpose, new bioinformatic tools for in silico identification of diagnostically relevant epitopes will be developed. This will render the diagnosis faster, less expensive and less time consuming and, at the same time, considerably more informative.

People involved: Konrad Sachse, Maximilian Collatz

Collaborations:

Grants: Zwanzig20 – InfectControl 2020: Molekulare Serologie zur schnellen Bestimmung der Impftiter gegen impf-präventable Infektionskrankheiten (STIKO-Liste) bei Migranten und anderen Patientengruppen; Subproject: STIKO-Serologie

Related publications:

[bibtex file=https://raw.githubusercontent.com/rnajena/literature/master/webpage_literature.bib key=Collatz:20] [bibtex file=https://raw.githubusercontent.com/rnajena/literature/master/webpage_outgroup.bib key=Sachse:18]

Limiting viral outbreaks with Machine Learning

Zoonosis, the natural transmission of infections from animal to human, is a far-reaching global problem, occurring more often due to globalization. In case of a virus outbreak, it is helpful to know which host organism was the original carrier of the virus, so people can be separated from this hosts. The sooner this happens, the greater the chances of limiting an outbreak.
As a fast method of predicting the original host, we are working on the ability to predict the host of a virus based on the viral genome sequence. Due to the lack of knowledge about virus adaptation, it is difficult to find practical features for machine learning methods. With this in mind, we apply deep learning methods because they do not require predefined features and are one of todays most powerful machine learning methods.

People involved: Florian Mock, Adrian Viehweger

Related publications:

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Viruses in groundwater

The principle aim of the CRC AquaDiva is to increase our understanding of the links between surface and subsurface, especially how organisms inhabiting the subsurface critical zone reflect and influence their physical, ecological and geochemical environment. In project A06, we will determine the diversity of previously known viruses in groundwater by high-throughput sequencing of viral genomes. A challenge in virology is the identification of previously undetected viruses, which we will tackle with our new approach of virus assembly. We complement the approach by investigating the differences of metatranscriptomes of the different sampling sites. Finally, we will determine the broadly unknown virus decay in groundwater to gain insights in communication pauses with other organisms.

People involved: Christian Höner zu Siederdissen, Akash Srivastava, Sebastian Krautwurst, Muriel Ritsch, Milena Žarković

Collaborations: Kirsten Küsel, Antonis Chatzinotas, René Kallies, Christian Jogler

Grants: CRC 1076 — AquaDiva: A6: Viral Diversity, Viral de novo Assembly, and Viral Decay in Groundwater

Related publications:

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Towards solving the puzzle of aging

Aging is still an enigma, which has challenged scientists and philosophers for centuries. For example, individuals within one species or population show a divers range of life spans (most humans die around 80 years of age, whereas some reach the age of 100 or even more). Which genes are responsible for this variance in lifespan and how exactly is aging caused? We try to help answer these questions by the means of transcriptomic data analysis, including the identification of genes and biological processes that are differentially regulated through time, in different species and tissues.

People involved: Emanuel BarthAkash Srivastava

Collaborations: Alessandro Cellerino, Otto Witte

Grants: RegenerAging — Analyzing the regulation of aging

Related publications:


Ecology and Species Barriers in Emerging Viral Diseases

Emerging viruses existing in animal reservoirs may cause epidemic or epizootic diseases if transmitted to humans or livestock. While we understand the pathogenicity and epidemiology of prototypic emerging viral diseases, we know little about mechanisms driving virus emergence from animal reservoirs. To move ahead, we need to generalise our view on emerging viruses, taking into consideration the ecology of viruses in their natural reservoirs. We hypothesise that small mammals, mainly bats and rodents, constitute most relevant virus reservoirs due to their large group sizes, population density, mixing and turnover, as well as their exposure to arthropod vectors.

People involved: Martin Hölzer, Nelly Fernanda Mostajo Berrospi

Collaborations: Christian Drosten, Friedemann Weber, Stephan Becker, Martin Beer, Georg Kochs

Grants: DFG SPP 1596: Ecology and Species Barriers in Emerging Viral Diseases

Related publications:

[bibtex file=https://raw.githubusercontent.com/rnajena/literature/master/webpage_literature.bib key=Mostajo:19,Hölzer:19a,Hölzer:19,Gerst:18,Fuchs:17,Hoelzer:16]

 RNA structures and functions in viruses

Non coding RNAs (ncRNA) are known regulatory elements in organisms from all kingdoms. The secondary structure of RNA is often linked to its function. When looking at a viral genome (especially an RNA genome) it only makes sense that viruses make strong use of ncRNAs to bypass the host’s immune response, to regulate their own genes or to stop the gene expression of the host genes. We are concerned with the analysis of conserved RNA structures in well described virus families and the de novo prediction of potentially functional structural elements in less known families. We use combinations of machine learning, clustering and homology based methods. The identification of functional structural elements could help to develop new antiviral therapies in the future, as important replication mechanisms of the virus can be disturbed.

People involved: Kevin Lamkiewicz, Gabriel Lovate

Related publications: 

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The role of non-coding RNAs in human placental development

Inside the placenta, the fetal syncytiotrophoblast forms the interface between fetus and mother, from which exosomes and microvesicles are permanently released into the maternal circulation. These particles contain fetal proteins and ncRNAs for communication with neighbouring and distant maternal cells. The number, size and content of these particles may reflect or predict placental disorders. Several severe pregnancy pathologies, including preeclampsia, are human-specific and their pathomechanisms are not yet understood.
To date, most examples of ncRNAs that have been identified to be specific for fetal tissues, such as the placenta, are members of the group of microRNAs (miRNAs). Long ncRNAs have only been marginally investigated. We need to expand the knowledge about ncRNAs in the placenta and ncRNAs released from it to revolutionize the understanding of regulation processes inside the placenta and of fetal-maternal communication.

People involved: Sebastian Krautwurst

Collaborations: Udo Markert, Diana Maria Morales Prieto

Grants: DFG MA 5082/9-1: Embryonale nicht-kodierende RNAs in der menschlichen Plazenta und dem mütterlichen Blutkreislauf

Related publications: 

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Antibiotic resistance in the Ganges river valley

Antibiotics increasingly fail to treat a growing number of medical conditions due to antimicrobial resistance. This trend is especially acute in developing countries such as India, where broad resistances are known to have emerged. It is known that densely populated cities can drive the emergence and spread of antimicrobial resistance through for example industrial production sites, wastewater management practices and other cultural characteristics. Proximity to waterways or associated water collections seems especially relevant.
To identify controllable drivers of resistance emergence and spread we investigate two cities on the river Ganges in India – Allahabad and Kanpur. We also investigate the effect of human interference by analyzing samples before and after Kumbh Mela, which is by far the largest religious gathering in Prayagraj. This will allow us to discern naturally occurring resistance from resistance created by humans.

People involved: Akash Srivastava, Marie Lataretu

Collaborations: Ziauddin Ahammad Shaikh, Adrian Viehweger

Grants: BMBF – DBT Cooperative Science Program: Development of metagenomics assisted surveillance tools for tracking antibiotic resistance in river bodies — A study in the Ganges river valley (NANOLOG)


Statistical modeling of genomic and transcriptomic data

In the last two decades in the biotechnological area, one revolutionary advancement was chased by another, leading the life sciences into the big data era. However, besides the availability of vast amounts of different biological data, we still lack sufficient statistical models and methods to accurately process and evaluate these data. We aim to develop specialised statistical tools in the context of genomics (e.g., fuzzy k-meres) and transcriptomics (e.g., accurate modeling of read count distributions). We work on different aspects of statistical analysis, starting from the theoretical problem formulation, to the implementation of statistical models and the appropriated visualisation of results.

People involved: Emanuel Barth


Finding mitogenomes in fungi using short-read NGS data

Mitochondria are essential energy producing cell organelles in eukaryotes. Their genomes are common objects for phylogenetic studies. For fungi, mitochondria play also a key role for pathogenicity and drug resistance. The structure and evolution of the mitogenomes differs between plants, animals and fungi, whereby fungal mitogenomes have been less studied than in plants or animals. The loss of tRNAs and ribosomal proteins has been reported in fungal mitogenome, as well as recombination and variable gene distribution. Hence de novo tools for reconstructing the mitogenome in silico should work with as few information from related species as possible. We will develop a pipeline to find and annotate mitogenomes of fungal short-read NGS data automatically.

People involved: Marie Lataretu

Collaborations: Matthias Bernt


Multiplex-sequencing for different kingdoms 

The concept of the German Centre for Integrative Biodiversity Research (iDiv) encompasses the detection of biodiversity, understanding its emergence, exploring its consequences for ecosystem functions and services, and developing strategies to safeguard biodiversity under global change.
To record biological diversity is fundamental but faces many challenges. To analyse genomes and transcriptomes from all organisms e.g. in soil or gut of insects, we usually use different (wet-lab) extraction protocols for bacteria, fungi and viruses. Sometimes also a common host needs to be sequenced. Instead of sequencing about 10 times the same sample from different extraction protocols to obtain the complete biodiversity, we aim to develop a method to multiplex organisms from different kingdoms into one sequencing approach.

People involved: Franziska Hufsky

Grants: DFG iDiv: All-in-one Multiplex-Sequencing