Multiomics to Mechanisms Best Poster Awards

The EMBO|EMBL Symposium: Multiomics to Mechanisms: Challenges in Data Integration took place virtually 15 – 17 September 2021. With over 400 participants, this was the biggest multi-omics conference since it began in 2017. We had 96 posters presented virtually, and are excited to share the research from the three best poster prize winners. 

Identification of transcription factor signaling molecules by coupling gene expression and metabolomics

A portrait picture of Daniela Ledezma‑Tejeida
Daniela Ledezma‑Tejeida, ETH Zurich, Switzerland (Photo credit: Stefania Laddage)

Abstract

Bacteria need to adapt to changes in their environment in order to survive. Transcription factors (TFs) bind metabolites that signal such changes and in turn alter gene expression. Escherichia coli has the best characterized transcriptional regulatory network involving 300 predicted TFs, of which ~75% have a metabolite‑binding domain. However, the binding partners of only 95 TFs have been identified due to low-throughput of common in vitro identification methods. Here, we combined metabolomics and gene expression data obtained in vivo across several growth conditions to identify TF‑metabolite interactions of four TFs without a known binding partner: CdaR, CsgD, FlhDC and GadX. We have validated our method by accurately predicting the known binding partners of ArgR, TyrR and CysB, three highly studied TFs. The in vivo nature of our approach can not only identify new TF‑metabolite interactions but also provide insight into the most functionally relevant.

View Daniela’s poster

Towards topology‑based multi‑omics pathway enrichment and its application in toxicology

A portrait picture of Sebastian Canzler, Helmholtz‑Centre for Environmental Research
Sebastian Canzler, Helmholtz‑Centre for Environmental Research ‑ UFZ, Germany

Abstract

The call for an application of (multi‑)omics data in toxicology became highly prominent in recent years, since omics experiments are intended to generate comprehensive information on molecular changes in cells and tissues more quickly, more accurately, and with fewer resources than ever before. The associated hopes explicitly include the reduction of live animal testing and an increased number of analyzed substances that can be tested. Therein, multi‑omics data are essential to comprehensively infer mechanistic knowledge on molecular response pathways to subsequently guide and aid chemical risk assessment. However, currently available multi‑omics pathway enrichment methods struggle to cope with different aspects hampering their application in computational toxicology, e.g., the utilization of insufficient enrichment methods, missing support for time‑ and concentration resolved data, and restrictions on the pathway sources. Most approaches utilize a sequential data integration and thereby completely ignore the connections between different omics layers. With ToPaFC, we present the first step towards a consistent and simultaneous multi-omics-based pathway enrichment that accounts for those obstacles and explicitly takes the underlying pathway topology into account. Right now, we can deal with up to eight different pathway databases and two omics layers (trans/meta or prot/meta). The pathway topology is reflected in two different ways: i) the importance of a node (omics feature) is measured based on its connections and its relative localization within the pathway and ii) the influence of each node on the network is specified by the weight of its outgoing edges, whether they are inhibiting, neutral, or activating. With this integration of edge information along the pathway, our method inherently accounts for consistent molecular changes of the features. The derived node‑centered pathway representation is combined with measured multi‑omics features to calculate a topology‑based pathway fold change that accounts for consistent changes within the molecular response.

View Sebastian’s Poster

Computational approaches to scrutinize results from spatial proteomics of operable pancreatic cancer and neighboring tissue

A portrait picture of Ábel Szkalisity, University of Helsinki, Finland
Ábel Szkalisity, University of Helsinki, Finland

Abstract

The advance of laser‑microdissection technologies coupled with proteomics enables unprecedented insights into tissue proteomes. However, the limited availability of patient materials coupled with the high dimensional output of proteomics necessitates data integration across studies to safeguard the reliability of the results. We microdissected morphologically benign and neoplastic pancreas and surrounding stromal areas from 14 patients with early pancreatic ductal adenocarcinoma and analyzed their protein compositions with nLC‑MS/MS. The results indicated downregulated digestive functions in the malignant exocrine tissue and lower metabolic activity in the stroma vs. exocrine pancreas. Intriguingly, the majority of the most significant proteins for survival originated from the morphologically benign exocrine regions, suggesting that these areas may harbor early, predisposing changes. To scrutinize this idea, we compared their proteomes to proteomics data of 12 healthy control pancreatic samples obtained from publications. The protein identification and quantification pipeline from the raw mass spectrometer files were standardized to minimize variation introduced by search engines or protein sequence databases. Altogether, we identified 7,099 proteins in 67 samples involving 5 tissue types from 2 experiments and 5 batches. We investigated two independent strategies for rendering the values comparable. First, batch effects within experiments were corrected for with ComBat and the abundances across experiments were aligned with housekeeping protein normalization. However, this approach required full observations, removing over 90% of the identified proteins from the analysis. Hence, our second approach involved applying Group Factor Analysis to directly extract factors that reveal relationships between the tissue types in our study without compromising the protein coverage. These approaches not only showed that our main results are independent of the data analysis pipeline but also implicated changes in the mRNA splicing machinery as important players in pancreatic cancer. By surveying 165 patients from The Cancer Genome Atlas we revealed that increased transcriptional complexity indeed associates with poor survival in this disease.

View Ábel’s Poster

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Best poster awards – BioMalPar XVII

This year,  the BioMalPar conference took place for the 17th time, but the second time virtually. Three poster presenters stunned their peers with their visually attractive digital posters, presentations and research insights. Out of 90 posters, they received the best poster award by popular vote. Meet the winners!

Sex-specific genetic screens identify hundreds of Plasmodium fertility genes essential for the transmission of malaria parasites

Claire Sayers, Umea University, Sweden

Abstract

Sexual reproduction of malaria parasites is essential for their transmission by mosquitoes. Biological processes required for Plasmodium fertility include the formation of gametocytes, their transformation into gametes in response to signals from the mosquito, fertilisation in the bloodmeal, meiosis, and the formation of an invasive ookinete. Stage-specific gene expression data suggest that hundreds of parasite genes are uniquely required for sexual reproduction, but previous gene knockout studies have merely scratched the surface of this important aspect of parasite biology. We have mutagenised P. berghei lines that make only fertile male or only fertile female gametocytes, with barcoded PlasmoGEM vectors to screen >1200 targetable genes for sex-specific phenotypes. Our screens identify hundreds of genes with sex-specific roles. The data recapitulate existing knowledge of Plasmodium fertility and assign functions to previously unannotated genes. For the first time, we are gaining an unbiased picture of the molecular mechanisms of Plasmodium fertility at genome-scale, which will lead to a deeper understanding of this novel biology that could serve as targets for transmission blocking drugs or vaccines.

View Claire Sayers’ poster

ABCI3 confers pleiotropic drug resistance to antimalarial compounds

Emma Carpenter, Wellcome Sanger Institute, UK

Abstract

Understanding the mechanisms available to the malaria parasite for acquiring multidrug resistance will be important for predicting which genes may become important for clinical resistance in the future.
ABC transporters are an important protein family with roles in drug resistance across a variety of organisms, and mutations in PfMDR1 modulate sensitivity to multiple antimalarials. Several other ABC transporters are encoded in the Plasmodium genome, and we have identified mutations in ABCI3 that confer resistance to several experimental antimalarial compounds.
Using in vitro drug selection regimes with a set of four chemically related compounds (SY4, 10, 11, 13), we isolated 12 drug resistant lines that were subjected to whole genome sequencing. All contained either single nucleotide variants (SNVs) or copy number amplifications of abci3. The point mutations were located in or near predicted transmembrane domains, consistent with a role in modifying the substrate specificity of the transporter, and testing of these lines against other compounds chemically-unrelated to the SY series identified a subset to which sensitivity is also affected.

In addition, natural variants of ABCI3 are observed at or near to these putative resistance SNVs, and preliminary evidence indicates differing sensitivities to the SY compounds among field isolates and common lab strains that may be driven by variation in ABCI3.

This work suggests abci3 should be among the genes monitored for changes in prevalence in longitudinal sampling of field isolates.

View  Emma Carpenters’ Poster

Characterization of a new malaria vaccine candidate against Plasmodium vivax using genetically modified rodent malaria parasites

Diana Moita, Instituto de Medicina Molecular João Lobo Antunes, Portugal

Abstract

Malaria, a mosquito-borne disease caused by Plasmodium parasites, is the most prevalent parasitic infection worldwide. Despite considerable efforts, there is still no effective vaccine against human-infective Plasmodium parasites, of which P. falciparum (Pf) and P. vivax (Pv) are the clinically most significant. Whole-sporozoite (Wsp) vaccines, which induce efficient immune responses against the pre-erythrocytic (PE) stages of Plasmodium parasites, are among the most promising immunization strategies so far. Although most malaria vaccine research has focused on Pf infection, Pv continues to be the most widespread of the human-infective Plasmodium species, imposing significant health and economic burdens on affected countries. Importantly, Pv can originate dormant parasitic liver forms – hypnozoites – which may cause malaria relapses long after mosquito transmission. Recently, our lab developed a new Wsp based on the use of transgenic rodent P. berghei (Pb) parasites as a platform to deliver immunogens of human-infective Plasmodium parasites. Since our in silico studies predict that >60% of CD8+ T cell epitopes encoded in both the Pv and Pb proteomes are shared between these two parasites, we generated a new genetically modified Pb expressing the highly immunogenic circumsporozoite (CS) protein from Pv (PvCS), in addition to its endogenous CS, Pb(PvCS@UIS4), to be used as a vaccine candidate against Pv malaria. Our immunofluorescence microscopy studies confirmed that both the endogenous PbCS and the inserted PvCS are expressed during the PE stages of this transgenic parasite, and that its infectivity is similar to that of its wild-type (WT) counterpart. Specifically, the ability of Pb(PvCS@UIS4) to infect Anopheles stephensi mosquitoes, as measured by the number of oocysts or sporozoites formed, as well as its ability to infect and develop normally in mouse hepatocytes and red blood cells showed no significant differences from those observed for WT parasites. Subsequent studies showed that mice immunization with Pb(PvCS@UIS4) elicits the production of anti-PvCS antibodies that efficiently recognize and bind to Pv sporozoites. Considering the lack of efficient strategies to tackle Pv, this study represents a crucial step on the development of a new Wsp vaccine candidate against this parasite.

View Diana Moita’s poster

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Best Poster Awards — Chromatin and Epigenetics

The 10th edition of the EMBL Conference: Chromatin and Epigentics took place virtually this year. We welcomed more than 800 participants, from which 3 were selected best poster award winners prior to the meeting and who gave a short talk on the last day of the conference. Get a glimpse of their research.

Sequence-dependent surface condensation of pioneer transcription factor on DNA

Sina Wittmann, Max Planck Institute for Molecular Cell Biology and Genetics, Germany
Presenter: Sina Wittmann, Max Planck Institute for Molecular Cell Biology and Genetics, Germany

Abstract: Biomolecular condensates are dense assemblies of proteins that are dynamic and provide distinct biochemical compartments without being surrounded by a membrane. Some, such as P granules and stress granules, behave as droplets, have many millions of molecules, and are well described by a classic phase separation picture. Others, such as transcriptional condensates are thought to form on surfaces such as DNA, are small and contain thousands of molecules. However, the correct physical description of small condensates on DNA surfaces is still under discussion. Here we investigate this question using the pioneer transcription factor Klf4. We show that Klf4 can phase separate on its own at concentrations that are above physiological, but that at lower concentrations, Klf4 only forms condensates on DNA. Analysis using optical tweezers shows that these Klf4 condensates form on DNA by a switch-like transition from a thin adsorbed layer to a thick condensed layer that is well described as a prewetting transition on a heterogeneous substrate. Condensate formation of Klf4 on DNA is thus a form of surface condensation mediated by and limited to the DNA surface. Furthermore, we are investigating how Klf4 condensation is regulated by the property of the surface such as through DNA methylation. We speculate that the prewetting transition orchestrated by pioneer transcription factors underlies the formation of transcriptional condensates in cells and provides robustness to transcription regulation.

View poster.

Single-cell profiling of histone post-translational modifications and transcription in mouse and zebrafish differentiation systems

Presenter: Kim de Luca,  Hubrecht Institute, The Netherlands
Presenter: Kim de Luca,  Hubrecht Institute, The Netherlands

Abstract: During organism development and cellular differentiation, gene expression is carefully regulated at many levels. To that end, various epigenetic mechanisms translate cell-intrinsic and -extrinsic cues into activation and repression of the relevant parts of the genome. One of the most studied and versatile forms of epigenetic regulation is the post-translational modification (PTM) of the histone proteins around which DNA is wrapped. Histone PTMs affect the surrounding DNA by forming a binding platform for a range of effector proteins, as well as by directly modulating the biophysical properties of the chromatin. Hence, histone PTMs play a crucial role in priming, establishing, and maintaining transcriptional output and cell state. Many techniques used to study histone PTMs require thousands to millions of cells, and consequently mask the heterogeneity inherent to complex biological systems. To understand the nuanced relationship between chromatin context and transcription, single-cell and multi-modal approaches are necessary. We have previously developed a method to simultaneously measure transcriptional output and DNA-protein contacts by single-cell sequencing (scDam&T). This multi-modal method is particularly suitable for studying systems containing many transient cellular states. Here, we apply scDam&T to measure chromatin modifications by expressing the E. coli DNA adenine methyltransferase (Dam) fused to a domain that specifically recognizes a histone PTM. First, we validate this approach in population and single-cell samples by comparing the resulting data to orthogonal state-of-the-art techniques. Next, using mouse embryoid bodies as an in vitro differentiation system, we apply our method to deconvolve the lineage-specific regulation of Polycomb chromatin. Finally, we study the role of H3K9me3-marked heterochromatin in the developing zebrafish embryo.

Poster not available due to unpublished data, however, you can watch a short talk presentation here.

 

Presenter: Moushumi Das, University of Bern, Switzerland
Presenter: Moushumi Das, University of Bern, Switzerland

Poster and abstract not available due to unpublished data.

 

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Best Poster Awards – The Identity and Evolution of Cell Types

The second edition of the EMBO | EMBL Symposium: The Identity and Evolution of Cell Types brought together an increased number of researchers from this growing community. 315 scientists joined the virtual meeting and enjoyed four days of talks and poster presentations streamed live. A total of 72 posters were presented at the two live poster sessions out of which three were selected as the best posters by popular vote. Take a look at the winners and their work.

Molecular fingerprinting sea anemones and jellyfish: A transcriptomic approach to characterize Cnidarian cell types
image of Alison Cole
Alison Cole, University of Vienna, Austria

Presenter: Alison Cole, University of Vienna, Austria

Abstract

Animals typically consist of hundreds of different cell types, yet the evolutionary mechanisms underlying the emergence of new cell types are unclear. Cnidarians offer advantages to studies of metazoan cell type evolution, as they are the sister group to the Bilateria and yet comprise an extremely diverse set of lineages that exhibit variable life history strategies, life spans, regenerative properties, animal-defining cell types (ie. muscles and neurons), as well as clade-specific cell types (i.e. cnidocytes). Advances in single cell RNA sequencing have opened the frontiers for molecular profiling of cell types at a genome-wide scale. Application of these technologies for comparisons across species remains in its infancy, and is largely, but not exclusively, restricted to closely related species with well-defined orthologous gene sets. Here we present a large single cell dataset derived from the anthozoan polyp Nematostella vectensis (comprising both developmental and tissue-derived samples),the scyphozoan moon jelly (Aurelia aurita; comprising all life history stages as well as medusa tissue-derived samples), and the hydrozoan Clytia hemispherica (young medusa only). The same cell complement that is identifiable from species-specific genome-wide analyses is recoverable using only a set of 1:1:1 orthologous genes in all three species. Analyses of the reduced gene matrix combining all three species robustly identifies putatively homologous cell types amongst the neurosecretory derivatives, as well as cell populations with clear species-specific transcriptomic profiles. Interpretations of these data in the light of specific cell types will be discussedin order to demonstrate that the combination of unbiased single cell transcriptomes and gene-directed validations can permit the identification of novel and conserved cell types.

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Stylophora pistillata cell atlas illuminates stony coral symbiosis, calcification and immunity
Anamaria Elek, Centre for Genomic Regulation, Spain

Presenter: Anamaria Elek, Centre for Genomic Regulation, Spain

Abstract

Stony corals are colonial cnidarians that sustain the most biodiverse marine ecosystems on Earth: coral reefs. Life cycle of these animals involves a swimming larva that settles and metamorphoses into a sessile polyp, which in turn develops into the adult stage, depositing in the process a protein rich organic matrix and extracellular calcium carbonate crystals to form a stony skeleton. Despite their ecological importance, little is known about the cell types and molecular pathways that underpin the biology of reef-building corals. Using single-cell RNA sequencing, we have defined over 40 cell types across the three life stages of a stony coral Stylophora pistillata. Among others, we characterized previously unknown coral immune cells, endosymbiont alga-hosting cells, and calicoblasts responsible for calcium-carbonate skeleton formation in both settling polyp and the adult coral. Apart from these specialized coral cell types, we identified evolutionary conserved cell types by phylogenetic integration of our S. pistillata cell atlas with three other available cnidarian species. These evolutionary conservations include neuronal and gland cell types, cnidaria-specific cnidocytes, and others. Overall, this study reveals the molecular and cellular basis of stony coral biology, and addresses the evolution of cell type programs in three major cnidarian lineages separated by 500 million years of evolution.

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Gene family evolution underlies cell type diversification in the hypothalamus of teleosts*
Maxwell Shafer, Biozentrum, University of Basel, Switzerland

Presenter: Maxwell ShaferBiozentrum, University of Basel, Switzerland

Abstract

Hundreds of cell types form the vertebrate brain, but it is largely unknown how similar these cellular repertoires are between or within species, or how cell type diversity evolves. To examine cell type diversity across and within species, we performed single-cell RNA sequencing of ~130,000 hypothalamic cells from zebrafish (Danio rerio) and surface- and cave-morphs of Mexican tetra (Astyanax mexicanus). We found that over 75% of cell types were shared between zebrafish and Mexican tetra, which last shared a common ancestor over 150 million years ago. Orthologous cell types displayed differential paralogue expression that was generated by sub-functionalization after genome duplication. Expression of terminal effector genes, such as neuropeptides, was more conserved than the expression of their associated transcriptional regulators. Species-specific cell types were enriched for the expression of species-specific genes, and characterized by the neo-functionalization of members of recently expanded or contracted gene families. Within species comparisons revealed differences in immune repertoires and transcriptional changes in neuropeptidergic cell types associated with genomic differences between surface- and cave-morphs. The single-cell atlases presented here are a powerful resource to explore hypothalamic cell types, and reveal how gene family evolution and the neo- and sub-functionalization of paralogs contribute to cellular diversity.

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*https://doi.org/10.1101/2020.12.13.414557 


Working on your own conference poster? Then check out these 8 tips for preparing a digital poster that stands out from the crowd.

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Best Poster and Artwork Awards — VIZBI 2021: Visualizing Biological Data

The 11th international meeting on Visualizing Biological Data, best known as VIZBI, was held virtually this year. The conference was as exciting as always, filled with great discussions, an outstanding speaker line-up and of course amazing, beautiful visuals.

The participants had the chance to vote for their favourite scientific poster and artwork — a very tough choice as all of the works were truly amazing! Here, we present you the winners.

Best scientific poster

Building a whole cell in 3D

by  Martina Maritan (The Scripps Research Institute, USA) Ludovic Autin, Jonathan Karr, Markus Covert, Arthur Olson, David Goodsell.

Martina Maritan, The Scripps Research Institute, USA
Martina Maritan

Mesoscale 3D models are powerful tools for exploring structural data across the entire range of scales, from the molecular to the cellular level. We built structural mesoscale models of a whole Mycoplasma genitalium (MG) cell with the CellPACK suite using data generated from a whole-cell MG simulation. 3D models integrate structural details into a computational model of MG, highlighting specific properties of the ingredients, and creating snapshots of the cell at defined time points of the simulations. Our modeling process goes through three steps. Firstly, we assemble a recipe: a list of all the proteins of Mycoplasma associated with a structural representation. Secondly, we create a model of the genome with DNA, RNA, RNA polymerase, mRNA, and ribosomes, with user-defined location of RNA polymerase and length of transcripts. Thirdly, we assemble the nucleoid, soluble, and membrane ingredients, and relax the whole system to resolve steric overlaps. The result is a framework for interactive construction of atomic resolution mesoscale models describing a spatial view of a whole bacterial cell. Our models are the first atomistic representation of an entire bacterial cell.

Building a whole cell in 3D
Building a whole cell in 3D

View Martina Maritan’s poster
Watch lightning talk

Second best scientific poster

How to communicate cell behaviours visually

by Christian StolteCellarity, USA.

Christian Stolte, Cellarity, USA
Christian Stolte

Cellarity is pioneering a new approach to drug discovery, treating disease at the level of the cell as opposed to a single molecular target. Combining unique expertise in network biology, high-resolution single-cell sequencing data, and machine learning, the result is a new understanding of the cell’s trajectory from health to disease, and how cells relate to one another in tissues. The cell and its network of transcripts and proteins offer a more complete view of the complexity of human biology than any individual molecular target. To help communicate this, we use visualizations resembling a cityscape called ‘Cellarity maps’. Based on the UMAP dimensionality reduction technique, they use the third dimension (height) to show density. This creates landscapes where we can now use colour to encode additional dimensions, and make it easier to see different ‘cell behaviours.’

How to communicate cell behaviours visually
How to communicate cell behaviours visually

View Christian Stolte’s poster
Watch lighting talk

Best artwork

10 Hallmarks of cancer

by Karolína Kryštofová, Institute of Biophysics of the Czech Academy of Sciences, Czech Republic.

Karolína Kryštofová, Institute of Biophysics of the Czech Academy of Sciences Czech Republic
Karolína Kryštofová

A whimsical series of illustrations inspired by the hallmarks of cancer as described by Weinberg & Hanahan in their paper Hallmarks of cancer: the next generation (2011).

10 Hallmarks of cancer
10 Hallmarks of cancer

View Karolína Kryštofová’s artwork

Second best artwork

The human heart

by Philipp Dexheimer, Research Institute of Molecular Pathology, Austria.

Philipp Dexheimer, Research Institute of Molecular Pathology, Austria
Philipp Dexheimer

Inspired by Leonardo Da Vinci’s original way of depicting his science and ideas, this digital painting illustrates the 21st century research process to understand formation of such a delicate organ as the human heart. Cells are derived, self-organize into 3-dimensional organoid structures, and allow unique insight into heart development and physiology. Illustrating research described in: Hofbauer et al., BioRxiv, 2020 – Cardioids reveal self-organizing principles of human cardiogenesis.

The human heart

View Philipp Dexheimer’s artwork

If you’d like to take a look at all of the posters presented at VIZBI 2021, you can! Visit the poster gallery, dive into the science, enjoy the beautiful images and be amazed by the scientists’ visualization skills.

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