MOTIVATION: The compartmentalization of biochemical reactions, involved in the activation of gene expression in the eukaryotic nucleus, leads to the formation of membraneless bodies through liquid-liquid phase separation. These formations, called transcriptional condensates, appear to play important roles in gene regulation as they are assembled through the association of multiple enhancer regions in 3D genomic space. To date, we are still lacking efficient computational methodologies to identify the regions responsible for the formation of such condensates, based on genomic and conformational data. RESULTS: In this work, we present SEGCOND, a computational framework aiming to highlight genomic regions involved in the formation of transcriptional condensates. SEGCOND is flexible in combining multiple genomic datasets related to enhancer activity and chromatin accessibility, to perform a genome segmentation. It then uses this segmentation for the detection of highly transcriptionally active regions of the genome. At a final step, and through the integration of Hi-C data, it identifies regions of putative transcriptional condensates (PTCs) as genomic domains where multiple enhancer elements coalesce in 3D space. SEGCOND identifies a subset of enhancer segments with increased transcriptional activity. PTCs are also found to significantly overlap highly interconnected enhancer elements and super enhancers obtained through two independent approaches. Application of SEGCOND on data from a well-defined system of B-cell to macrophage transdifferentiation leads to the identification of previously unreported genes with a likely role in the process. AVAILABILITY AND IMPLEMENTATION: Source code and details for the implementation of SEGCOND is available at https://github.com/AntonisK95/SEGCOND. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Anti-TNF agents have been in the first line of treatment of various inflammatory diseases such as Rheumatoid Arthritis and Crohn's Disease, with a number of different biologics being currently in use. A detailed analysis of their effect at transcriptome level has nevertheless been lacking. We herein present a concise analysis of an extended transcriptomics profiling of four different anti-TNF biologics upon treatment of the established hTNFTg (Tg197) mouse model of spontaneous inflammatory polyarthritis. We implement a series of computational analyses that include clustering of differentially expressed genes, functional analysis and random forest classification. Taking advantage of our detailed sample structure, we devise metrics of treatment efficiency that take into account changes in gene expression compared to both the healthy and the diseased state. Our results suggest considerable variability in the capacity of different biologics to modulate gene expression that can be attributed to treatment-specific functional pathways and differential preferences to restore over- or under-expressed genes. Early intervention appears to manage inflammation in a more efficient way but is accompanied by increased effects on a number of genes that are seemingly unrelated to the disease. Administration at an early stage is also lacking in capacity to restore healthy expression levels of under-expressed genes. We record quantifiable differences among anti-TNF biologics in their efficiency to modulate over-expressed genes related to immune and inflammatory pathways. More importantly, we find a subset of the tested substances to have quantitative advantages in addressing deregulation of under-expressed genes involved in pathways related to known RA comorbidities. Our study shows the potential of transcriptomic analyses to identify comprehensive and distinct treatment-specific gene signatures combining disease-related and unrelated genes and proposes a generalized framework for the assessment of drug efficacy, the search of biosimilars and the evaluation of the efficacy of TNF small molecule inhibitors.

This volume of Bioinformatics includes the proceedings papers of the 17th European Conference in Computational Biology (ECCB), an annual international Conference for research in computational biology and bioinformatics. The Conference is being held jointly with ISMB in the odd-numbered years and independently in the even-numbered years. This year, the 17th ECCB (ECCB 2018) will take place in Athens, at the Stavros Niarchos Foundation Cultural Center (SNFCC), from September 8 to 12, 2018. SNFCC, which was opened in June 2017, is a multifunctional arts, education and entertainment complex located on the edge of Faliro Bay, 4.5 km south of the center of Athens. Information on the ECCB 2018 can be found at eccb18.org and will be later archived at www.ebi.ac.uk/eccb/2018/. With more than 1,000 participants from academia and industry, ECCB is the leading European Conference on computational biology and bioinformatics and the second largest internationally, next to ISMB (Intelligent Systems in Molecular Biology). The work presented in ECCB is related to all domains of the field of computational biology and bioinformatics, ranging from molecular level to systems biology level. The proceedings papers present new computational methodologies and tools for addressing challenging problems in the field, including research in single cell high-throughput data, microbiome data, 3 D organization of the genome, and others. The Conference also includes Highlights presentations, which showcase important papers published over the last year. Since 2016, it also features an Applications track that presents computational biology work applied in industry, clinics, governmental organizations, and other fields beyond academia. ECCB meetings are held every year in a different European country. In odd-numbered years, ECCB is co-organized with the ISMB Conference, which is held in Europe. Previous meetings were organized in Prague, Czech Republic (Beerenwinkel and Bromberg, 2017, ISMB/ECCB 2017); The Hague, Netherlands (Heringa and Reinders, ECCB 2016); Dublin, Ireland (Moreau and Beerenwinkel, 2015, ISMB/ECCB 2015); Strasbourg, France (Devignes and Moreau, 2014, ECCB 2014); Berlin, Germany (Ben-Tal, 2013, ISMB/ECCB 2013); Basel, Switzerland (Schwede and Iber, 2012, ECCB 2012); Vienna, Austria (Gaasterland and Vingron, 2011, ISMB/ECCB 2011); Ghent, Belgium (Moreau and Heringa, 2010, ECCB 2010); Stockholm, Sweden (Gusfield and Tramontano, 2009, ISMB/ECCB 2009); Cagliari, Italy (Tramontano, 2008, ECCB 2008); Vienna, Austria (Lengauer et al., 2009, ISMB/ECCB 2007); Eilat, Israel (Wolfson and Safer, 2006, ECCB 2006); Madrid, Spain (Guigo et al., 2005, ECCB 2005); Glasgow, United Kingdom (Thornton et al., 2004, ISMB/ECCB 2004); Paris, France (Lenhof and Sagot, 2003, ECCB 2003); and Saarbrücken, Germany (Lengauer, 2002). ECCB 2018 continues the 16-year tradition and is held under the auspices of the Hellenic Society for Computational Biology and Bioinformatics (HSCBB; www.hscbb.gr), which promotes bioinformatics research and training in Greece since 2009. HSCBB organizes an annual conference in a different Greek city each time (e.g., Athens, Thessaloniki, Alexandroupolis, Patras, Lamia, Heraklion), aiming to provide exposure to new field developments to graduate students and researchers. The broad participation in the annual HSCBB conferences (more than 130 participants each year) show that the bioinformatics community in Greek universities and research centers has now matured significantly. HSCBB has also a strong international presence in the field of computational biology. It is an observer in the Greek ELIXIR consortium and is affiliated with the International Society for Computational Biology (ISCB) and Global Organization for Bioinformatics Learning, Education & Training (GOBLET). The organization of ECCB 2018, along with the European Student Council Symposium 2018 (see below), inspired the formation this year of the Greek chapter of the ISCB Student Council. ECCB 2018 received a record high number of 280 applications for proceedings talks from institutions from 48 countries. The submissions were organized in five themes, according to their topic: (1) Data (organization, integration, knowledge discovery, multi-scale modeling), (2) Genes (expression, function, editing, geno/phenotype), (3) Genome (sequence analysis, evolution, phylogeny, microbiome), (4) Proteins and Structural Biology (structure, function, alterations, drug design), and (5) Systems (molecular pathways, signaling, metabolomics). All proceedings submissions were subjected to a rigorous peer-review process (2-4 reviews per paper), organized by the members of the Programme Committees of the corresponding theme. The Programme Committees consisted of a Theme Chair (Michael Krauthammer, Roderic Guigo, Martin Vingron, Ivet Bahar, Alfonso Valencia, respectively) and two to four co-chairs (depending on the number of submissions assigned to this Theme). For the review, the EasyChair system (www.easychair.org) was used by 398 reviewers, recruited by the Programme Committees. Reviewers evaluated the impact and reproducibility of the presented research, as well as its suitability for the ECCB audience. Once the review was completed, the committee chairs and co-chairs selected 48 papers to be included in the ECCB 2018 proceedings (acceptance rate: 17%), with the number of papers accepted in each being proportional to the number of submissions initially assigned to this Theme. These papers required minor revisions and the authors had two weeks to modify them accordingly. All Proceedings Track papers and any supplementary files accompanying them are freely available in the electronic form of Oxford University Press journal Bioinformatics, as a special issue of September 2018. Together with the Proceedings track ECCB 2018 features 24 Highlights talks about scientific work already published in high impact science journals. They are coordinately presented and managed across the five themes with the proceeding presentations. We continued with newly established Application and ELIXIR tracks with 15 Applications talks, and 12 ELIXIR talks, all of which were selected after review. The aim of the Application track is to give a voice to those who apply computational biology in industry, clinics, governmental organizations, and other fields beyond academia. The aim of the ELIXIR Track is to showcase to the community the latest outputs and services from across the initiative. The presentations focus on developments relating to services and infrastructure within ELIXIR. ECCB 2018 also features a Poster Track, with 617 accepted posters, in which researchers present their latest findings in the corresponding thematic areas (Data, Genes, Genome, Proteins and Structural Biology, Systems). Seven distinguished keynote speakers will present their work: Prof. Bonnie Berger from the Massachusetts Institute of Technology (MIT), Prof. Christos Davatzikos from University of Pennsylvania, Prof. John Ioannidis from Stanford University, Prof. Manolis Kellis from MIT, Prof. Jose Onuchic from Rice University, Dr. Janet Thornton, Director Emeritus of the European Bioinformatics Institute (EMBL-EBI), and Dr. Eleftheria Zeggini from the German Research Center for Environmental Health (GmbH). Furthermore, ECCB 2018 is hosting for the first time three special invited talks before the lunch breaks and a joint keynote talk. The invited speakers will present the funding opportunities of the European Research Council (ERC) funding mechanisms (Dr. Maria Siomos) and a talk on the ISCB Student Council Internship Program (Farzana Rahman). The joint keynote will be about ELIXIR: A Common European Infrastructure for Bioinformatics Research presented by the ELIXIR director Dr. Niklas Blomberg. For the first time in ECCB 2018, ELIXIR organizes eight short workshops, namely ELIXIR TeSS Usability Study, Beacons, BioSchemas, Galaxy, OpenEbench Fnd Bio.tools, Research under the GDPR, Implementation of DMPs and Data Stewardship in practice, Secure access to your services using ELIXIR AAI. The 5th European Student Council Symposium (ESCS) is taking place before the main conference organized by the Student Council of the ISCB (chair Daniele Parisi from KU Leuven and co-chair Yvonne Saara Gladbach from Rostock University). ESCS highlights will be published in F1000Research via the ISCB Student Council channel. For the first time the ISCB Student Council will present also an invited talk as stated above. We are really thankful to the ISCB Student Council for their enthusiasm, hard work and genuine scientific interest, which has made the ESCS an inseparable part of ECCB. During the ECCB 2018, ten exhibitor booths of all sizes will be set up on the Exhibit Hall floor, next to the central Conference venue and close to the Poster session and lunch area, namely: ELIXIR, BioExcel, EMBL-EBI, ERC, ISCB and ISCB Student Council, Goblet, Oxford University Press, Cambridge University Press, Peer Community In. The booths will be grouped together in a way that provides an enhanced networking environment for our exhibitors and delegates. Exhibitors will showcase the latest trends in computational biology and bioinformatics technology, in scientific literature, as well as in modelling and simulation. We invite participants to visit the exhibition area and support these community-minded organizations, who deliver a strong message in supporting the Computational Biology and Bioinformatics scientific field. The weekend before the conference 8 workshops (including two from Special Interest Groups – SIGs) and 13 Tutorials will take place. The aim of workshops is to provide participants the opportunity to discuss different perspectives on the cutting edge of a selected research field, through presenting technical issues, exchanging research ideas and sharing practical experiences. The two SIGs and six workshops preceding the ECCB 2018 main conference were selected out of a total of 12 applications, running all but one for a single day: (SIG-1) BioExcel 2nd SIG Meeting: Advanced Simulations for Biomolecular Research organized by Rossen Apostolov (KTH Royal Institute of Technology in Stockholm, Sweden), Zoe Cournia (Biomedical Research Foundation of the Academy of Athens, Greece), Vera Matser, (EMBL-EBI, UK), Anastas Mishev (UKIM Saints Cyril and Methodius University of Skopje, Republic of Macedonia), Hrachya Astsatryan (Institute for Informatics and Automation Problems, Armenia), Adam Carter (EPCC, UK) (SIG-2): Intrinsically disordered proteins: advances and state-of-the-art of the field organized by Silvio Tosatto (University of Padua, Italy), Zsuzsanna Dosztanyi (Eötvös Loránd University, Hungary), Norman Davey (University College Dublin, Ireland), Damiano Piovesan (University of Padua, Italy) (W1) Computational Epigenomics a two-day workshop organized by Yassen Assenov (German Cancer Research Center, Germany), Guido Sanguinetti (University of Edinburgh, UK), Jordana Bell (King’s College London, UK), Jörn Walter (Saarland University, Germany), Christoph Bock (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Austria) and Verena Wolf (Saarland University, Germany) (W2) BioNetVisA 2018 workshop: From biological network reconstruction to data visualization and analysis in molecular biology and medicine organized by Inna Kuperstein (Institut Curie, France), Emmanuel Barillot (Institut Curie, France), Andrei Zinovyev (Institut Curie, France), Luis Cristobal Monraz Gomez (Institut Curie, France), Hioraki Kitano (RIKEN Center for Integrative Medical Sciences, Japan), Minoru Kanehisa (Institute for Chemical Research, Kyoto University, Japan), Samik Ghosh (Systems Biology Institute, Tokyo, Japan), Nicolas Le Novère (Babraham Institute, UK), Robin Haw (Ontario Institute for Cancer Research, Canada), Alfonso Valencia (Spanish National Bioinformatics Institute, Madrid, Spain), Lodewyk Wessels (Netherlands Cancer Institute, Amsterdam, Netherlands), Patrick Kemmeren (Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands) (W3) CPW2018: Computational Pathology Workshop—second edition organized by Yves Sucaet (Vrije Universiteit Brussel, Belgium), Jeroen Van der Laak (UMC Radboud, Netherlands), Zev Leifer (New York College of Podiatric Medicine, USA), Yukako Yagi (Memorial Sloan Kettering Cancer Center, USA), Raphaël Marée (Université de Liège, Belgium), David Ameisen (IRIF, CNRS and Université Paris Diderot, France), Paul Van Diest (UMC Utrecht, Netherlands), Jeffrey Fine (Magee-Womens Hospital of UPMC) (W4) Interactive visualizations to guide health diagnostics and personalized medicine organized by Dimitrios Tzovaras, Konstantinos Votis and Kostas Stamatopoulos (all at Information Technologies Institute of the Center for Research and Technology Hellas, Greece) (W5) Logical modelling of cellular networks organized by Anna Niarakis (Univ Evry, Université Paris-Saclay, France) and Denis Thieffry (Ecole Normale Supérieure, Paris, France). (W6) Recent Computational Advances in Metagenomics organized by Valentin Loux, Mahendra Mariadassou, Pierre Peterlongo and Sophie Schbath (all at INRA, France) The purpose of the ECCB tutorial program is to provide participants with lectures and hands-on training to the most important and emerging topics in bioinformatics and computational biology research. The tutorials offer skills ranging from early and basic steps of computational analysis in recently introduced topics to advanced computational skills in important established topics. A total of thirteen ECCB 2018 tutorials running for half or a full day will be held at ECCB 2018. These were selected out of sixteen applications: (T1) Automated Machine Learning for Bioinformatics and Computational Biology organized by Ioannis Tsamardinos (University of Crete, Greece; Gnosis Data Analysis, Greece), Kleio Maria Verrou (University of Crete, Greece) and Vincenzo Lagani (Ilia State University, Georgia; Gnosis Data Analysis, Greece) (T2) Computational Mass Spectrometry with OpenMS—From Algorithms to Integrated Workflows organized by Julianus Pfeuffer (Freie Universität Berlin, Germany) and Timo Sachsenberg (Universität Tübingen, Germany) (T3)—Write your own R script to jointly analyze RNA-, ATAC-seq, DNA methylation, SNPs and find drug targets in signal transduction networks using TRANSFAC® organized by Philip Stegmaier (geneXplain GmbH, Germany), Olga Kel-Margoulis (geneXplain GmbH, Germany), Alexander Kel (geneXplain GmbH, Germany; Institute of Systems Biology, Russia) (T4) Deep learning for predicting protein–DNA and –RNA binding organized by Yaron Orenstein (Ben-Gurion University, Israel) (T5) Delving into non-coding RNA with RNAcentral and Rfam. Organized by Anton Petrov and Ioanna Kalvari (both at EMBL-EBI, UK) (T6) DIANA Tools and Databases: In silico investigation of miRNA functions organized by Artemis Hatzigeorgiou, Spyros Tastsoglou, Dimitra Karagkouni, Nikos Perdikopanis, Giorgos Skoufos, Ioannis Kavakiotis (all at University of Thessaly, Greece) (T7) Exploring programmatic access to Protein sequence, function and structure with UniProt and PDBe organized by Andrew Nightingale and Mihaly Varadi (both at EMBL-EBI, UK) (T8) Fifth International Hands-on Tutorial on Logical Modelling: Exploring the dynamics of biological systems organized by Tomas Helikar (University of Nebraska, USA) and Juilee Thakar (University of Rochester Medical Center, USA) (T9) From an application to a fully integrated workflow—Comprehensive software engineering with SeqAn organized by René Rahn and Hannes Hauswedell (both at Freie Universität Berlin, Germany) (T10) Hands-on on Protein Function Prediction with Machine Learning and Interactive Analytics organized by Rabie Saidi and Tunca Dogan (EMBL-EBI, UK) (T11) Single-cell RNA-Seq Data Analysis organized by Panagiotis Papasaikas (Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland; Swiss Institute of Bioinformatics, Switzerland) and Atul Sethi (Friedrich Miescher Institute for Biomedical Research (FMI), Basel, Switzerland; University Hospital Basel, University of Basel, Switzerland; Swiss Institute of Bioinformatics, Switzerland) (T12) Modern and scalable tools for efficient analysis of very large metagenomic datasets organized by Alexander Sczyrba (Bielefeld University, Germany), Christian Henke (Bielefeld University, Germany), Clovis Galiez (MPI for Biophysical Chemistry, Germany), Milot Mirdita (PI for Biophysical Chemistry, Germany) and Johannes Soeding (MPI for Biophysical Chemistry, Germany) (T13) User Experience Design for Computational Biologists organized by Nikiforos Karamanis and Xavier Watkins (both at EMBL-EBI, UK) Finally, following the tradition of ECCB, a number of travel fellowships, sponsored by ISCB, were given to young participants. We received 103 applications from scientists from 31 countries. After careful review and consideration, we awarded 14 travel fellowships, mainly to PhD students from nine countries that had an accepted proceedings paper. Volunteering is another important way for young scientists to visit and support the conference, as well as connect with other young scientists. The skills, talent and dedication of the volunteers are expected to largely contribute to the overall quality of the Conference. We made our best to accept all 91 applicants from 16 countries who were eligible to attend the Conference at a very low registration fee. Next to the volunteers, we would like to thank all the people who helped through their work to make this Conference a success. The Theme Chairs and Co-chairs as well all the reviewers who have been the heart of the Conference and helped selecting excellent papers, making thus this Conference a success. We are truly indebted to them. We are also grateful to the ECCB Steering Committee for their advice and continuous the of the organization of ECCB 2018. This conference would be at all the support from Anna Steering Committee and Chair ECCB our application and advice about to make a of was It was our to and inspired by for science with to in a will be in our and in our During the one year of the conference the support of Steering Committee Chair ECCB ECCB and Yves ECCB 2010, ECCB was Yves and for your continuous and We are also grateful to the ISCB Society for Computational for their and in ECCB 2018 at the international level and for This Conference would be the support of our and ELIXIR level and BioExcel was our level Cambridge University Press, Oxford University Press, Community and were ISCB, the Student Council of the ISCB, and who as exhibitors at ECCB 2018 also A thank to all for their and for to make ECCB 2018 an and Conference. A number of people to the organization of ECCB 2018. They beyond their of for making this conference really Maria a as was for the the the venue the and was for and Panagiotis was for the technical support of the registration Dr. organized the members of the DIANA also this Spyros Tastsoglou, Dimitra Karagkouni, Perdikopanis, Dimitrios Finally, the of a conference is its presentations, the conference for its participants. We thank all of for to ECCB 2018. We will the and in the city of Athens, the city and were of

BACKGROUND: Under both physiological and pathological conditions gene expression programs are shaped through the interplay of regulatory proteins and their gene targets, interactions between which form intricate gene regulatory networks (GRN). While the assessment of genome-wide expression for the complete set of genes at a given condition has become rather straight-forward and is performed routinely, we are still far from being able to infer the topology of gene regulation simply by analyzing its "descendant" expression profile. In this work we are trying to overcome the existing limitations for the inference and study of such regulatory networks. We are combining our approach with state-of-the-art gene set enrichment analyses in order to create a tool, called Regulatory Network Enrichment Analysis (RNEA) that will prioritize regulatory and functional characteristics of a genome-wide expression experiment. RESULTS: RNEA combines prior knowledge, originating from manual literature curation and small-scale experimental data, to construct a reference network of interactions and then uses enrichment analysis coupled with a two-level hierarchical parsing of the network, to infer the most relevant subnetwork for a given experimental setting. It is implemented as an R package, currently supporting human and mouse datasets and was herein tested on one test case for each of the two organisms. In both cases, RNEA's gene set enrichment analysis was comparable to state-of-the-art methodologies. Moreover, through its distinguishing feature of regulatory subnetwork reconstruction, RNEA was able to define the key transcriptional regulators for the studied systems as supported from the literature. CONCLUSIONS: RNEA constitutes a novel computational approach to obtain regulatory interactions directly from a genome-wide expression profile. Its simple implementation, with minimal requirements from the user is coupled with easy-to-parse enrichment lists and a subnetwork file that may be readily visualized to reveal the most important components of the regulatory hierarchy. The combination of prior information and novel concept of a hierarchical reconstruction of regulatory interactions makes RNEA a very useful tool for a first-level interpretation of gene expression profiles.