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XTRAS

eXplainable TRanslational AI in Space

Principal Investigator: Prof. Dr. Stefan Simm, Universität Greifswald

Project Collaborators :

AI collaborators:

More About XTRAS

Milestones:
1) Development of a transparent CNN for Clever Hans predictors
2) Modular NN for biomarkers and pathways
3) Development of a trustworthy DNN for the creation of a regulatory model

The central goal of the XTRAS single project is to implement explainable deep learning architectures with layerwise relevance propagation (LRP) to recognise biomarkers for microgravity influences in order to facilitate data analysis of high-throughput datasets in different organisms (plants and animals). Based on omics datasets, different levels of molecular interaction (transcriptome, proteome) and their interplay under microgravity in plants and animals will be used for classification. In addition, modular neural networks (NN) will be used to analyse the importance of individual genes and their interaction within important metabolic pathways, e.g. gravitropism in plants or metastasis in humans. In addition, images of roots from FLUMIAS microscope experiments will be automatically analyzed and preprocessed to identify different patterns for the differentiation of longitudinal microgravity experiments.
In both cases, methods for background noise reduction, confounding factor identification and processing and balancing steps will be developed that take into account the small number of replicates and their high variability in life science experiments. In parallel, an explainable AI method for linking heterogeneous data (microscope images, omics expression values, sequence/structure information) will be implemented to detect causal links for microgravity influences in human and plants.

Schematic representation of the milestones (M1.1 – M3.1) and their breakdown into work packages. The experimental datasets of the collaborating groups ASIM0V and AMCRIS are in the Omics expression datasets and in the microscopy image datasets. The partners involved in the exchange are listed in the grey boxes of the work packages.
(A) Graphical user interface of the Voronoi-Treeraiser software including, (B) Interactive user interface for dynamic labelling of metabolic pathways and individual genes/proteins. (C) Illustration of the integration of proteomics and transcriptomics in a Voronoi Treemap based on the proteomaps hierarchy. Zoom into the metabolic pathway of glycolysis to visualise the change of proteome and transcriptome during pollen development.
(A) Schematic representation of the modular neural network and its inputs. Each circle stands for an individual module representing a part of the KEGG Brite hierarchy and the expression values from Omics experiments. (B) The LRP indicates the importance for classification (control or stress/disease) for individual genes and metabolic pathways (modules). blue = unimportant genes/metabolic pathways; orange = important genes/metabolic pathways.

Our Team


Prof. Dr. Stefan Simm

XTRAS Principal Investigator
University Medicine Greifswald
Coburg University of Applied Science and arts

Jan Oldenburg

XTRAS Research Assistant
University Medicine Greifswald

Publications

2024

Shanmugam, Thiruvenkadam; Chaturvedi, Palak; Streit, Deniz; Ghatak, Arindam; Bergelt, Thorsten; Simm, Stefan; Weckwerth, Wolfram; Schleiff, Enrico

Low dose ribosomal DNA P-loop mutation affects development and enforces autophagy in Arabidopsis. Journal Article

In: RNA biology, vol. 21, iss. 1, pp. 1-15, 2024, ISSN: 1555-8584.

Abstract | Links | BibTeX

2023

Bergquist, Timothy; Schaffter, Thomas; Yan, Yao; Yu, Thomas; Prosser, Justin; Gao, Jifan; Chen, Guanhua; Charzewski, Łukasz; Nawalany, Zofia; Brugere, Ivan; Retkute, Renata; Prusokas, Alidivinas; Prusokas, Augustinas; Choi, Yonghwa; Lee, Sanghoon; Choe, Junseok; Lee, Inggeol; Kim, Sunkyu; Kang, Jaewoo; Mooney, Sean D; Guinney, Justin; Consortium, Patient Mortality Prediction DREAM Challenge

Evaluation of crowdsourced mortality prediction models as a framework for assessing artificial intelligence in medicine. Journal Article

In: Journal of the American Medical Informatics Association : JAMIA, vol. 31, iss. 1, pp. 35-44, 2023, ISSN: 1527-974X.

Abstract | Links | BibTeX

Dunkel, Heiko; Wehrmann, Henning; Jensen, Lars R; Kuss, Andreas W; Simm, Stefan

MncR: Late Integration Machine Learning Model for Classification of ncRNA Classes Using Sequence and Structural Encoding. Journal Article

In: International journal of molecular sciences, vol. 24, iss. 10, 2023, ISSN: 1422-0067.

Abstract | Links | BibTeX

2022

Gast, Martina; Nageswaran, Vanasa; Kuss, Andreas W; Tzvetkova, Ana; Wang, Xiaomin; Mochmann, Liliana H; Rad, Pegah Ramezani; Weiss, Stefan; Simm, Stefan; Zeller, Tanja; Voelzke, Henry; Hoffmann, Wolfgang; Völker, Uwe; Felix, Stefan B; Dörr, Marcus; Beling, Antje; Skurk, Carsten; Leistner, David-Manuel; Rauch, Bernhard H; Hirose, Tetsuro; Heidecker, Bettina; Klingel, Karin; Nakagawa, Shinichi; Poller, Wolfram C; Swirski, Filip K; Haghikia, Arash; Poller, Wolfgang

tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions. Journal Article

In: Cells, vol. 11, iss. 24, 2022, ISSN: 2073-4409.

Abstract | Links | BibTeX

Nath, Neetika; Simm, Stefan

Machine Learning Based Methods and Best Practices of microRNA-Target Prediction and Validation. Journal Article

In: Advances in experimental medicine and biology, vol. 1385, pp. 109-131, 2022, ISSN: 0065-2598.

Abstract | Links | BibTeX

Jagirdar, Gayatri; Elsner, Matthias; Scharf, Christian; Simm, Stefan; Borucki, Katrin; Peter, Daniela; Lalk, Michael; Methling, Karen; Linnebacher, Michael; Krohn, Mathias; Wolke, Carmen; Lendeckel, Uwe

Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression. Journal Article

In: Frontiers in genetics, vol. 13, pp. 931017, 2022, ISSN: 1664-8021.

Abstract | Links | BibTeX

Gather, Leonie; Nath, Neetika; Falckenhayn, Cassandra; Oterino-Sogo, Sergio; Bosch, Thomas; Wenck, Horst; Winnefeld, Marc; Grönniger, Elke; Simm, Stefan; Siracusa, Annette

Macrophages Are Polarized toward an Inflammatory Phenotype by their Aged Microenvironment in the Human Skin. Journal Article

In: The Journal of investigative dermatology, vol. 142, iss. 12, pp. 3136-3145.e11, 2022, ISSN: 1523-1747.

Abstract | Links | BibTeX

Fester, Niclas; Zielonka, Elisabeth; Goldmann, Jakob; Frombach, Ann-Sophie; Müller-Kuller, Uta; Gutfreund, Niklas; Riegel, Kristina; Smits, Jos G A; Schleiff, Enrico; Rajalingam, Krishnaraj; Zhou, Huiqing; Simm, Stefan; Dötsch, Volker

Enhanced pro-apoptosis gene signature following the activation of TAp63α in oocytes upon γ irradiation. Journal Article

In: Cell death & disease, vol. 13, iss. 3, pp. 204, 2022, ISSN: 2041-4889.

Abstract | Links | BibTeX

2020

Keller, Mario; Schleiff, Enrico; Simm, Stefan

miRNAs involved in transcriptome remodeling during pollen development and heat stress response in Solanum lycopersicum. Journal Article

In: Scientific reports, vol. 10, iss. 1, pp. 10694, 2020, ISSN: 2045-2322.

Abstract | Links | BibTeX

Hu, Yangjie; Fragkostefanakis, Sotirios; Schleiff, Enrico; Simm, Stefan

Transcriptional Basis for Differential Thermosensitivity of Seedlings of Various Tomato Genotypes. Journal Article

In: Genes, vol. 11, iss. 6, 2020, ISSN: 2073-4425.

Abstract | Links | BibTeX

2019

Berz, Jannik; Simm, Stefan; Schuster, Sebastian; Scharf, Klaus-Dieter; Schleiff, Enrico; Ebersberger, Ingo

HEATSTER: A Database and Web Server for Identification and Classification of Heat Stress Transcription Factors in Plants. Journal Article

In: Bioinformatics and biology insights, vol. 13, pp. 1177932218821365, 2019, ISSN: 1177-9322.

Abstract | Links | BibTeX

2018

Keller, Mario; Consortium, SPOT-ITN; Simm, Stefan

The coupling of transcriptome and proteome adaptation during development and heat stress response of tomato pollen. Journal Article

In: BMC genomics, vol. 19, iss. 1, pp. 447, 2018, ISSN: 1471-2164.

Abstract | Links | BibTeX

2017

Keller, M.; Hu, Y.; Mesihovic, A.; Fragkostefanakis, S.; Schleiff, E.; Simm, S.

Alternative splicing in tomato pollen in response to heat stress Journal Article

In: DNA Research, vol. 24, iss. 2, 2017, ISSN: 17561663.

Abstract | Links | BibTeX

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