E-Mail: jannes.spangenberg@uni-jena.de
Room: 4004
Phone: +49-3641-9-46485
Publications
2025
Meyer, Daria; Göttsch, Winfried; Spangenberg, Jannes; Stieber, Bettina; Krautwurst, Sebastian; Hoelzer, Martin; Brandt, Christian; Linde, Joerg; zu Siederdissen, Christian Höner; Srivastava, Akash; Zarkovic, Milena; Wollny, Damian; Marz, Manja
Unlocking the Full Potential of Nanopore Sequencing: Tips, Tricks, and Advanced Data Analysis Techniques Journal Article
In: bioRxiv, 2025.
@article{nokey,
title = {Unlocking the Full Potential of Nanopore Sequencing: Tips, Tricks, and Advanced Data Analysis Techniques},
author = {Daria Meyer and Winfried Göttsch and Jannes Spangenberg and Bettina Stieber and Sebastian Krautwurst and Martin Hoelzer and Christian Brandt and Joerg Linde and Christian {Höner zu Siederdissen} and Akash Srivastava and Milena Zarkovic and Damian Wollny and Manja Marz},
doi = {10.1101/2023.12.06.570356},
year = {2025},
date = {2025-01-27},
urldate = {2025-01-27},
journal = {bioRxiv},
abstract = {Nucleic acid sequencing is the process of identifying the sequence of DNA or RNA, with DNA used for genomes and RNA for transcriptomes. Deciphering this information has the potential to greatly advance our understanding of genomic features and cellular functions. In comparison to other available sequencing methods, nanopore sequencing stands out due to its unique advantages of processing long nucleic acid strands in real time, within a small portable device, enabling the rapid analysis of samples in diverse settings. Evolving over the past decade, nanopore sequencing remains in a state of ongoing development and refinement, resulting in persistent challenges in protocols and technology. This article employs an interdisciplinary approach, evaluating experimental and computational methods to address critical gaps in our understanding in order to maximize the information gain from this advancing technology. Here we present both overview and analysis of all aspects of nanopore sequencing by providing statistically supported insights. Thus, we aim to provide fresh perspectives on nanopore sequencing and give comprehensive guidelines for the diverse challenges that frequently impede optimal experimental outcomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nucleic acid sequencing is the process of identifying the sequence of DNA or RNA, with DNA used for genomes and RNA for transcriptomes. Deciphering this information has the potential to greatly advance our understanding of genomic features and cellular functions. In comparison to other available sequencing methods, nanopore sequencing stands out due to its unique advantages of processing long nucleic acid strands in real time, within a small portable device, enabling the rapid analysis of samples in diverse settings. Evolving over the past decade, nanopore sequencing remains in a state of ongoing development and refinement, resulting in persistent challenges in protocols and technology. This article employs an interdisciplinary approach, evaluating experimental and computational methods to address critical gaps in our understanding in order to maximize the information gain from this advancing technology. Here we present both overview and analysis of all aspects of nanopore sequencing by providing statistically supported insights. Thus, we aim to provide fresh perspectives on nanopore sequencing and give comprehensive guidelines for the diverse challenges that frequently impede optimal experimental outcomes.
2024
Spangenberg, Jannes; Mündnich, Stefan; Busch, Anne; Pastore, Stefan; Wierczeiko, Anna; Goettsch, Winfried; Dietrich, Vincent; Pryszcz, Leszek P.; Cruciani, Sonia; Novoa, Eva Maria; Joshi, Kandarp; Perera, Ranjan; Giorgio, Salvatore Di; Arrubarrena, Paola; Tellioglu, Irem; Poon, Chi-Lam; Wan, Yuk Kei; Göke, Jonathan; Hildebrandt, Andreas; Dieterich, Christoph; Helm, Mark; Marz, Manja; Gerber, Susanne; Alagna, Nicolo
The RMaP challenge of predicting RNA modifications by nanopore sequencing Journal Article
In: Communications Chemistry, vol. 8, iss. 1, 2024.
@article{nokey_79,
title = {The RMaP challenge of predicting RNA modifications by nanopore sequencing},
author = {Jannes Spangenberg and Stefan Mündnich and Anne Busch and Stefan Pastore and Anna Wierczeiko and Winfried Goettsch and Vincent Dietrich and Leszek P. Pryszcz and Sonia Cruciani and Eva Maria Novoa and Kandarp Joshi and Ranjan Perera and Salvatore Di Giorgio and Paola Arrubarrena and Irem Tellioglu and Chi-Lam Poon and Yuk Kei Wan and Jonathan Göke and Andreas Hildebrandt and Christoph Dieterich and Mark Helm and Manja Marz and Susanne Gerber and Nicolo Alagna},
doi = {10.1038/s42004-025-01507-0},
year = {2024},
date = {2024-12-04},
urldate = {2024-12-04},
journal = {Communications Chemistry},
volume = {8},
issue = {1},
abstract = {The field of epitranscriptomics is undergoing a technology-driven revolution. During past decades, RNA modifications like N6-methyladenosine (m6A), pseudouridine (ψ), and 5-methylcytosine (m5C) became acknowledged for playing critical roles in cellular processes. Direct RNA sequencing by Oxford Nanopore Technologies (ONT) enabled the detection of modifications in native RNA, by detecting noncanonical RNA nucleosides properties in raw data. Consequently, the field’s cutting edge has a heavy component in computer science, opening new avenues of cooperation across the community, as exchanging data is as impactful as exchanging samples. Therefore, we seize the occasion to bring scientists together within the RNA Modification and Processing (RMaP) challenge to advance solutions for RNA modification detection and discuss ideas, problems and approaches. We show several computational methods to detect the most researched mRNA modifications (m6A, ψ, and m5C). Results demonstrate that a low prediction error and a high prediction accuracy can be achieved on these modifications across different approaches and algorithms. The RMaP challenge marks a substantial step towards improving algorithms’ comparability, reliability, and consistency in RNA modification prediction. It points out the deficits in this young field that need to be addressed in further challenges.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The field of epitranscriptomics is undergoing a technology-driven revolution. During past decades, RNA modifications like N6-methyladenosine (m6A), pseudouridine (ψ), and 5-methylcytosine (m5C) became acknowledged for playing critical roles in cellular processes. Direct RNA sequencing by Oxford Nanopore Technologies (ONT) enabled the detection of modifications in native RNA, by detecting noncanonical RNA nucleosides properties in raw data. Consequently, the field’s cutting edge has a heavy component in computer science, opening new avenues of cooperation across the community, as exchanging data is as impactful as exchanging samples. Therefore, we seize the occasion to bring scientists together within the RNA Modification and Processing (RMaP) challenge to advance solutions for RNA modification detection and discuss ideas, problems and approaches. We show several computational methods to detect the most researched mRNA modifications (m6A, ψ, and m5C). Results demonstrate that a low prediction error and a high prediction accuracy can be achieved on these modifications across different approaches and algorithms. The RMaP challenge marks a substantial step towards improving algorithms’ comparability, reliability, and consistency in RNA modification prediction. It points out the deficits in this young field that need to be addressed in further challenges.
zu Siederdissen, Christian Höner; Spangenberg, Jannes; Bisdorf, Kevin; Krautwurst, Sebastian; Srivastava, Akash; Marz, Manja; Taubert, Martin
Nanopore sequencing enables novel detection of deuterium incorporation in DNA Journal Article
In: Computational and Structural Biotechnology Journal, vol. 23, 2024.
@article{nokey_74,
title = {Nanopore sequencing enables novel detection of deuterium incorporation in DNA},
author = {Christian {Höner zu Siederdissen} and Jannes Spangenberg and Kevin Bisdorf and Sebastian Krautwurst and Akash Srivastava and Manja Marz and Martin Taubert},
doi = {10.1016/j.csbj.2024.09.027},
year = {2024},
date = {2024-10-03},
urldate = {2024-10-03},
journal = {Computational and Structural Biotechnology Journal},
volume = {23},
abstract = {Identifying active microbes is crucial to understand their role in ecosystem functions. Metabolic labeling with heavy, non-radioactive isotopes, i.e., stable isotope probing (SIP), can track active microbes by detecting heavy isotope incorporation in biomolecules such as DNA. However, the detection of heavy isotope-labeled nucleotides directly during sequencing has, to date, not been achieved. In this study, Oxford nanopore sequencing was utilized to detect heavy isotopes incorporation in DNA molecules. Two isotopes widely used in SIP experiments were employed to label a bacterial isolate: deuterium (D, as D2O) and carbon-13 (13C, as glucose). We hypothesize that labeled DNA is distinguishable from unlabeled DNA by changes in the nanopore signal. To verify this distinction, we employed a Bayesian classifier trained on signal distributions of short oligonucleotides (k-mers) from labeled and unlabeled sequencing reads. Our results show a clear distinction between D-labeled and unlabeled reads, based on changes in median and median absolute deviation (MAD) of the nanopore signals for different k-mers. In contrast, 13C-labeled DNA cannot be distinguished from unlabeled DNA. For D, the model employed correctly predicted more than 85% of the reads. Even when metabolic labeling was conducted with only 30% D2O, 80% of the obtained reads were correctly classified with a 5% false discovery rate. Our work demonstrates the feasibility of direct detection of deuterium incorporation in DNA molecules during Oxford nanopore sequencing. This finding represents a first step in establishing the combined use of nanopore sequencing and SIP for tracking active organisms in microbial ecology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Identifying active microbes is crucial to understand their role in ecosystem functions. Metabolic labeling with heavy, non-radioactive isotopes, i.e., stable isotope probing (SIP), can track active microbes by detecting heavy isotope incorporation in biomolecules such as DNA. However, the detection of heavy isotope-labeled nucleotides directly during sequencing has, to date, not been achieved. In this study, Oxford nanopore sequencing was utilized to detect heavy isotopes incorporation in DNA molecules. Two isotopes widely used in SIP experiments were employed to label a bacterial isolate: deuterium (D, as D2O) and carbon-13 (13C, as glucose). We hypothesize that labeled DNA is distinguishable from unlabeled DNA by changes in the nanopore signal. To verify this distinction, we employed a Bayesian classifier trained on signal distributions of short oligonucleotides (k-mers) from labeled and unlabeled sequencing reads. Our results show a clear distinction between D-labeled and unlabeled reads, based on changes in median and median absolute deviation (MAD) of the nanopore signals for different k-mers. In contrast, 13C-labeled DNA cannot be distinguished from unlabeled DNA. For D, the model employed correctly predicted more than 85% of the reads. Even when metabolic labeling was conducted with only 30% D2O, 80% of the obtained reads were correctly classified with a 5% false discovery rate. Our work demonstrates the feasibility of direct detection of deuterium incorporation in DNA molecules during Oxford nanopore sequencing. This finding represents a first step in establishing the combined use of nanopore sequencing and SIP for tracking active organisms in microbial ecology.
2023
Hufsky, Franziska; Abecasis, Ana B.; Babaian, Artem; Beck, Sebastian; Brierley, Liam; Dellicour, Simon; Eggeling, Christian; Elena, Santiago F.; Gieraths, Udo; Ha, Anh D.; Harvey, Will; Jones, Terry C.; Lamkiewicz, Kevin; Lovate, Gabriel L.; Lücking, Dominik; Machyna, Martin; Nishimura, Luca; Nocke, Maximilian K.; Renard, Bernard Y.; Sakaguchi, Shoichi; Sakellaridi, Lygeri; Spangenberg, Jannes; Tarradas-Alemany, Maria; Triebel, Sandra; Vakulenko, Yulia; Wijesekara, Rajitha Yasas; González-Candelas, Fernando; Krautwurst, Sarah; Pérez-Cataluña, Alba; Randazzo, Walter; Sánchez, Gloria; Marz, Manja
The International Virus Bioinformatics Meeting 2023 Journal Article
In: Viruses, vol. 15, iss. 10, 2023, ISSN: 1999-4915.
@article{nokey_47,
title = {The International Virus Bioinformatics Meeting 2023},
author = {Franziska Hufsky and Ana B. Abecasis and Artem Babaian and Sebastian Beck and Liam Brierley and Simon Dellicour and Christian Eggeling and Santiago F. Elena and Udo Gieraths and Anh D. Ha and Will Harvey and Terry C. Jones and Kevin Lamkiewicz and Gabriel L. Lovate and Dominik Lücking and Martin Machyna and Luca Nishimura and Maximilian K. Nocke and Bernard Y. Renard and Shoichi Sakaguchi and Lygeri Sakellaridi and Jannes Spangenberg and Maria Tarradas-Alemany and Sandra Triebel and Yulia Vakulenko and Rajitha Yasas Wijesekara and Fernando González-Candelas and Sarah Krautwurst and Alba Pérez-Cataluña and Walter Randazzo and Gloria Sánchez and Manja Marz},
doi = {10.3390/v15102031},
issn = {1999-4915},
year = {2023},
date = {2023-09-30},
urldate = {2023-09-30},
journal = {Viruses},
volume = {15},
issue = {10},
abstract = {The 2023 International Virus Bioinformatics Meeting was held in Valencia, Spain, from 24–26 May 2023, attracting approximately 180 participants worldwide. The primary objective of the conference was to establish a dynamic scientific environment conducive to discussion, collaboration, and the generation of novel research ideas. As the first in-person event following the SARS-CoV-2 pandemic, the meeting facilitated highly interactive exchanges among attendees. It served as a pivotal gathering for gaining insights into the current status of virus bioinformatics research and engaging with leading researchers and emerging scientists. The event comprised eight invited talks, 19 contributed talks, and 74 poster presentations across eleven sessions spanning three days. Topics covered included machine learning, bacteriophages, virus discovery, virus classification, virus visualization, viral infection, viromics, molecular epidemiology, phylodynamic analysis, RNA viruses, viral sequence analysis, viral surveillance, and metagenomics. This report provides rewritten abstracts of the presentations, a summary of the key research findings, and highlights shared during the meeting.},
keywords = {},
pubstate = {published},
tppubtype = {article}
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The 2023 International Virus Bioinformatics Meeting was held in Valencia, Spain, from 24–26 May 2023, attracting approximately 180 participants worldwide. The primary objective of the conference was to establish a dynamic scientific environment conducive to discussion, collaboration, and the generation of novel research ideas. As the first in-person event following the SARS-CoV-2 pandemic, the meeting facilitated highly interactive exchanges among attendees. It served as a pivotal gathering for gaining insights into the current status of virus bioinformatics research and engaging with leading researchers and emerging scientists. The event comprised eight invited talks, 19 contributed talks, and 74 poster presentations across eleven sessions spanning three days. Topics covered included machine learning, bacteriophages, virus discovery, virus classification, virus visualization, viral infection, viromics, molecular epidemiology, phylodynamic analysis, RNA viruses, viral sequence analysis, viral surveillance, and metagenomics. This report provides rewritten abstracts of the presentations, a summary of the key research findings, and highlights shared during the meeting.
Spangenberg, Jannes; zu Siederdissen, Christian Höner; Žarković, Milena; Triebel, Sandra; Rose, Ruben; Christophersen, Christina Martínez; Paltzow, Lea; Hegab, Mohsen M.; Wansorra, Anna; Srivastava, Akash; Krumbholz, Andi; Marz, Manja
Magnipore: Prediction of differential single nucleotide changes in the Oxford Nanopore Technologies sequencing signal of SARS-CoV-2 samples Journal Article
In: bioRxiv, 2023.
@article{nokey,
title = {Magnipore: Prediction of differential single nucleotide changes in the Oxford Nanopore Technologies sequencing signal of SARS-CoV-2 samples},
author = {Jannes Spangenberg and Christian {Höner zu Siederdissen} and Milena Žarković and Sandra Triebel and Ruben Rose and Christina Martínez Christophersen and Lea Paltzow and Mohsen M. Hegab and Anna Wansorra and Akash Srivastava and Andi Krumbholz and Manja Marz},
doi = {10.1101/2023.03.17.533105},
year = {2023},
date = {2023-03-17},
urldate = {2023-03-17},
journal = {bioRxiv},
abstract = {Oxford Nanopore Technologies (ONT) allows direct sequencing of ribonucleic acids (RNA) and, in addition, detection of possible RNA modifications due to deviations from the expected ONT signal. The software available so far for this purpose can only detect a small number of modifications. Alternatively, two samples can be compared for different RNA modifications. We present Magnipore, a novel tool to search for significant signal shifts between samples of Oxford Nanopore data from similar or related species. Magnipore classifies them into mutations and potential modifications. We use Magnipore to compare SARS-CoV-2 samples. Included were representatives of the early 2020s Pango lineages (n=6), samples from Pango lineages B.1.1.7 (n=2, Alpha), B.1.617.2 (n=1, Delta), and B.1.529 (n=7, Omicron). Magnipore utilizes position-wise Gaussian distribution models and a comprehensible significance threshold to find differential signals. In the case of Alpha and Delta, Magnipore identifies 55 detected mutations and 15 sites that hint at differential modifications. We predicted potential virus-variant and variant-group-specific differential modifications. Magnipore contributes to advancing RNA modification analysis in the context of viruses and virus variants.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oxford Nanopore Technologies (ONT) allows direct sequencing of ribonucleic acids (RNA) and, in addition, detection of possible RNA modifications due to deviations from the expected ONT signal. The software available so far for this purpose can only detect a small number of modifications. Alternatively, two samples can be compared for different RNA modifications. We present Magnipore, a novel tool to search for significant signal shifts between samples of Oxford Nanopore data from similar or related species. Magnipore classifies them into mutations and potential modifications. We use Magnipore to compare SARS-CoV-2 samples. Included were representatives of the early 2020s Pango lineages (n=6), samples from Pango lineages B.1.1.7 (n=2, Alpha), B.1.617.2 (n=1, Delta), and B.1.529 (n=7, Omicron). Magnipore utilizes position-wise Gaussian distribution models and a comprehensible significance threshold to find differential signals. In the case of Alpha and Delta, Magnipore identifies 55 detected mutations and 15 sites that hint at differential modifications. We predicted potential virus-variant and variant-group-specific differential modifications. Magnipore contributes to advancing RNA modification analysis in the context of viruses and virus variants.