News

For the seminar on the 21st of September Mădălina Giurgiu invited Evangelia Petsalaki to talk about her research. If you are interested in joining write an e-Mail to compcancer at charite dot de to receive the zoom link.

Data-driven approaches towards studying context-specific cell signalling

Our group aims to understand and describe the organisation principles of cell signalling that allow the diverse and context-specific cell responses and phenotypes.

It is well established that signalling responses happen through complex networks. However, most signalling research still uses linear pathways as the ground truth. Moreover, signalling responses are highly dependent on context, such as tissue type, genetic background etc and therefore these static pathways are not always suitable. There is also a high bias in the literature towards kinases and pathways for which reagents and prior knowledge is readily available. This leaves a huge dark space in our understanding of cell signalling and significantly hinders studies of its general principles.

In this talk I will present two projects where we try to mitigate some of the above issues. For the first one I will present CEN-tools, an integrative webserver and python package, that allows users to navigate the contexts of different gene essentialities. I will demonstrate examples of its use in discovering new gene-gene relationships and important putative signalling targets for different cancers. I will also describe an extension of this project whereby we have developed a linear model to deconvolute the effect of different tissue types and driver cancer mutations on context specific essentiality. For the second one I will present a method that combines paired transcriptomics and imaging data to extract context-specific signalling networks, with the context in this case cell shape in breast cancer. The method is generalisable to any paired transcriptomics/phenotype data.

Short biography of Evangelia Petsalaki

I am originally from Athens Greece, where I also completed my undergraduate degree in Biology at the University of Athens, with a thesis on using neural networks for the prediction of protein subcellular location. I then moved to the EMBL in Heidelberg, where under the supervision of Rob Russell I did a PhD (2009) on structural bioinformatics predicting peptide binding on protein structures. My postdoc was done under the supervision of Tony Pawson and Fritz Roth where I worked on a diverse array of projects from Rho signalling, proteomics, phosphoproteomics to yeast genetics. Since 2017 I am a group leader at the EMBL-EBI and my group focuses on the study of the principles underpinning context specific cell signalling responses in humans.

The upcoming CompCancer Seminar will be hosted by Eleonora Usatikova. Find the invitation below. The link is available from compcancer at charite dot de.

Dear all,

I would like to invite you to the next CompCancer seminar, which will take place on 23.02. at 3 pm.

Our guest speaker will be Benjamin Auerbach, a Ph.D. student from the Laboratory for Statistical and Translational Genomics at the University of Pennsylvania. He will present his unpublished work on circadian phase inference in single cells.

Title of the talk: “Unsupervised Circadian Phase Inference in Single-Cell RNA-Sequencing Data”

The circadian clock is a 24-hour cellular timekeeping mechanism that temporally regulates human physiology. Single-cell RNA-sequencing (scRNA-seq) has been increasingly adopted to study circadian transcription. Nonetheless, scRNA-seq has mainly been applied to data generated over light-dark cycle time courses, in which cell collection time in the light-dark cycle is presumed to be a direct proxy for cell circadian time. This assumption limits using these data for the discovery of cell phase heterogeneity, its determinants (e.g. spatial location within a tissue), and its role in other cellular processes (e.g. gating cellular differentiation). Moreover, investigators may be interested in conducting single-sample scRNA-seq of unsynchronized cell populations, for which sample collection time is not a meaningful proxy of cell phase. One approach to break the reliance on sample collection time as a proxy for cell phase is to estimate cell phase from scRNA-seq data directly, a task referred to as unsupervised phase inference. While existing approaches have been developed for similar problems, such as cell cycle phase inference in scRNA-seq and circadian phase inference from bulk RNA-seq samples, these approaches yield poor circadian phase estimates in scRNA-seq. Moreover, existing approaches do not quantify estimation uncertainty, which is essential for result interpretation from highly sparse scRNA-seq data. We’ve developed an unsupervised phase inference algorithm, Tempo, to predict cell circadian time from scRNA-seq expression. Based on Bayesian variational inference, Tempo incorporates domain knowledge of the circadian clock to yield state-of-the-art circadian phase estimates and well-calibrated uncertainty quantifications. We further demonstrate these properties generalize to the cell cycle.

The upcoming CompCancer Seminar will be hosted by Madalina Giurgiu. Find the invitation below. The link is available from compcancer at charite dot de.

Dear all,

I would like to announce the next CompCancer Literature Seminar on Wednesday, 2nd February, at 11 am.

Our invited guest speaker is Elias Rodríguez Fos (PhD), an expert on complex structural rearrangements and somatic mutational patterns analysis. In this seminar, Elias will give a comprehensive introduction on mutational signatures and complex rearrangements in cancer, taking neuroblastoma, one of the most common pediatric malignancies, as an example. Further, he will show how we identified the mutational processes active in the development of this tumor and evaluate their impact on patients' clinical outcome.

Topic: Analyses of mutational signatures and complex rearrangements in cancer.  Understanding the mutational processes involved in neuroblastoma development and their clinical implications.

Abstract:
The activity of different endogenous and/or exogenous mutational processes, including replication errors, exposure to DNA damaging agents, and errors in DNA repair mechanisms, imprint characteristic patterns of mutations in the genome defined as mutational signatures. Recent analyses in multiple cancer types have extracted different mutational signatures associated with single-nucleotide variants, small insertions and deletions, copy number alterations, and patterns of structural variants involving multiple genomic regions such as extrachromosomal circular DNA, chromothripsis, and breakage-fusion-bridge cycles, amongst others. Some of these signatures are linked to known biological processes active in cancer, whereas others have yet unknown etiologies.
 

Elias's Bio:

Elias Rodriguez-Fos received his B.Sc. degree in Biology from the Universitat Autònoma de Barcelona (UAB), and his M.Sc. degree in Genetics and Genomics from the Universitat de Barcelona (UB). In 2020, he obtained his Ph.D. degree in Bioinformatics from the Universitat de Barcelona, studying the role of complex rearrangements in cancer at the computational genomics group, led by Dr. David Torrents in the Barcelona Supercomputing Center (BSC). During his Ph.D., he contributed to describing the role of extrachromosomal circular DNA as a genome remodeler. Currently, he is working as a Humboldt postdoctoral fellow in Dr. Anton Henssen's and Dr. Johannes Schulte's labs at the Charité/MDC in Berlin. His research focuses on the analysis of somatic mutational patterns from all variant classes, including complex structural variants, in neuroblastoma.

Feel free to share this link with anyone else who could be interested.
Looking forward to seeing many of you,

Madalina

On November 23rd 2021, Tincy defended her thesis “An Integrative Genetic, and Epigenetic Characterization of Pancreatic Neuroendocrine Neoplasms (PanNENs) defines Distinct Molecular Features of Endocrine- and Exocrine-like Subgroups”.

In her work, Tincy analyzed how two sub-entities of PanNENs – so called PanNETs and PanNECs, differ in their DNA methylation patterns and other molecular features. This is important, as high-grade PanNETs are often hard to distinguish from PanNECs by classical morphological analyses used in pathology, yet have a different prognosis and response to specific therapies. Further, Tincy’s work addresses the cell-of-origin of either entity.

The upcoming CompCancer Seminar will be hosted by Stefan Peidli. Find the invitation below. The link is available from compcancer at charite dot de.

Dear all,

I'm excited to announce next weeks CompCancer Literature Seminar (Wednesday 15.09.) with Louis Cammarata and Adit Radhakrishnan from the lab of Caroline Uhler. 

Due to different time zones, the seminar will be at 5pm instead of 10am.

Louis and Adit will introduce us to overparametrized autoencoders and present their latest work where they developed a causal drug repurposing pipeline. This pipeline first identifies relevant drug responses in the latent space of an overparametrized autoencoder fed with drug perturbation data from e.g. CMap. In the paper, they applied their pipeline for drug repurposing against COVID-19.

Best,

Stefan