3DAROC16


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3C-based data analysis, 3D reconstruction of chromatin folding and Nucleosome Dynamics

3DAROC16
10-14th October 2016
Instituto Gulbenkian de Ciência, Oeiras, Portugal
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This popular 4-day hands-on course on 3C-based data analysis and chromosome structure determination is jumping across scales and resolutions in this year’s edition with the support of the MuG project. A final 1-day session focused on coarse-grained DNA and chromatin dynamics as well as hands-on training on nucleR, a package for non-parametric nucleosome positioning, and nucleosome dynamics, has been incorporated.

 

Special funding opportunity:

Thanks to the generous contribution of the MuG – Multiscale complex Genomics Project, the participation fee can be reduced to Euro 50.00 to the FIRST three candidates that can show that they need support at the time of acceptance, by adding a letter with a strong reason for the need for funding.

 

Monday 10th-Thursday 13th October

3C-based data analysis and 3D reconstruction of chromatin folding

3C-based methods, such as Hi-C, produce a huge amount of raw data as pairs of DNA reads that are in close spatial proximity in the cell nucleus. In this course, participants will learn to use TADbit, a software designed and developed to manage all dimensionalities of the Hi-C data:

  1. 1D – Map paired-end sequences to generate Hi-C interaction matrices
  2. 2D – Normalize matrices and identify constitutive domains (TADs, compartments)
  3. 3D – Generate populations of structures which satisfy the Hi-C interaction matrices
  4. 4. 4D – Compare samples at different time points

Participants can bring- specific biological questions and/or their own 3C-based data to analyze during the course. At the end of the course, participants will be familiar with the TADbit software and will be able to fully analyze Hi-C data. Note: Although the TADbit software is central in this course, alternative software will be discussed for each part of the analysis.

 

Instructors:

Centro Nacional de Análisis Genómico (CNAG) and Center for Genomic Regulation (CRG), Barcelona, ES

 

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Marc A. Marti-Renom obtained a Ph.D. in Biophysics from the Universidad Autonoma de Barcelona where he worked on protein folding under the supervision of B. Oliva, F.X. Aviles and M. Karplus. After that, he went to the US for a postdoctoral training on protein structure modeling at the Sali Lab (Rockefeller University) as the recipient of the Burroughs Wellcome Fund fellowship. Later on, Marc was appointed Assistant Adjunct Professor at UCSF. Between 2006 and 2011, he headed of the Structural Genomics Group at the CIPF in Valencia (Spain). Currently, Marc is an ICREA research professor and leads the Structural Genomics Group at the National Center for Genomic Analysis – Centre for Genomic Regulation (CNAG-CRG) in Barcelona. His group is broadly interested on how RNA, proteins and genomes organize and regulate cell fate. Finally, Marc is an Associate Editor of the PLoS Computational Biology journal and has published over 75 articles in international peer-reviewed journals.

 

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François Serra: obtained his Degree in Biology, specialized in Physiology and Neurophysiology, his Master’s Degree in Structural genomics and bioinformatics (Strasbourg I Universty, France) and it’s PhD in Evolutionary Genomics in the Department of Bioinformatics at the CIPF (Valencia). He is now part of the Structural Genomic team of Marc Marti-Renom at CNAG and at CRG (Barcelona). His main research interests are grounded on comparative genomics and evolution with a special focus on the effect of evolution in the structural arrangement of genomes. He has taught MEPA and 3DMOG for GTPB, and also in similar courses at CIPF (Valencia, ES) and the Department of Genetics of the University of Cambridge (UK).

 

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Davide Baù obtained a Master degree in Chemistry at the University of Padua and completed a one-year course in bioinformatics at the University of Cologne. He then moved to the University College Dublin, where, in 2008, he got his PhD at the School of Computer Science and Informatics under the supervision of Dr. Gianluca Pollastri. His thesis focused on the development of an optimization algorithm that searched the space of protein C-alpha trace configurations under the guidance of a statistical potential based on features predicted by machine learning techniques. After his PhD, Davide moved to Dr. Marc Marti-Renom´s laboratory where he started to work on genomic domains and genome structures determination by integrating 3C-based and FISH data into the Integrative Modeling Platform (IMP). During this time, he developed the methods that led to the determination of the first high-resolution model of a human genomic region, the alpha-globin genomic domain, and of the first three-dimensional model of an entire bacterial genome, the Caulobacter Crescentus. He is currently involved in different collaborations that aim at determining the genome architecture of several organisms including Human, Yeast, Mycoplasma Pneumoniae, Fly and Mouse.moved to the University College Dublin, where, in 2008, he got his PhD at the School of Computer Science and Informatics under the supervision of Dr. Gianluca Pollastri. His thesis focused on the development of an optimization algorithm that searched the space of protein C-alpha trace configurations under the guidance of a statistical potential based on features predicted by machine learning techniques. After his PhD, Davide moved to Dr. Marc Marti-Renom’s laboratory where he started to work on genomic domains and genome structures determination by integrating 3C-based and FISH data into the Integrative Modeling Platform (IMP). During this time, he developed the methods that led to the determination of the first high-resolution model of a human genomic region, the alpha-globin genomic domain, and of the first three-dimensional model of an entire bacterial genome, the Caulobacter Crescentus. He is currently involved in different collaborations that aim at determining the genome architecture of several organisms including Human, Yeast, Mycoplasma Pneumoniae, Fly and Mouse.

 

Friday 14th October

Coarse-Grained DNA and Chromatin Dynamics

Hi-C experiments are suitable to describe chromatin properties on a Mb scale while the highest resolution of this experiment, a bin in the contact map has a resolution in the kb range (highest resolution per bin so far is 1kb (Rao et al. Cell. 2015)). To be able to look beyond kb resolution in genome dynamics, two coarse-grained models are introduced in this workshop. First of all, a coarse-grained DNA model is introduced where DNA is represented intrinsically at base pair level with an elastic potential representing interactions between adjacent base pairs. This model allows the user to probe sequence-specific properties of naked B-DNA of any desired sequence. This coarse-grained DNA model is extended towards kb-long chromatin chains by implementing nucleosomes between linker DNA. Like this base pair specific properties of long chromatin chains can be examined. The model is flexible: the user can input his specific sequence of DNA with the positions of the nucleosomes within this sequence and investigate chromatin properties. Overall this model allows to overcome the resolution limit of Hi-C experiments by testing base pair level properties of chromatin on a kb scale.

 

Instructors:

Institute for Research in Biomedicine (IRB Barcelona)

 

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Jürgen Walther obtained his B.Sc. degree at the University of Würzburg (Germany) in Physics and his master degree at the University of Texas at Austin (USA) in Physics with specialization in Biophysics. He is now working as a PhD student in the Molecular modeling and bioinformatics laboratory of Modesto Orozco at the Institute for Research in Biomedicine Barcelona. His main focus is developing a coarse-grained model to simulate large pieces of chromatin with a very high resolution. His model is a component of the Multiscale Genomics project where a unified view of the genome at all length scales from base-pair to chromosome in form of a webserver is developed.

 

Nucleosome positioning and nucleosome Dynamics

nucleR is an R package that allows analysis of MNase-seq and ChIP-seq data and performs peak calling and nucleosome positioning. On the other hand, Nucleosome Dynamics is also an R package that works with MNase-seq data and focuses on comparing different MNase-seq experiments detect changes and zones where the chromatin is more dynamic. Both packages can be either used as R packages in a local R installation or from a web-based front end available online.

 

Instructors:

Institute for Research in Biomedicine (IRB Barcelona)

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Ricard Illa obtained his degree in Biochemistry at Universitat Autònoma de Barcelona and his Master’s degree on Bioinformatics on the same university. He is currently a PhD student in the Molecular Modeling and Bioinformatics group at Institute for Research in Biomedicine (Barcelona) under the supervision of Dr. Modesto Orozco. His main interests include the analysis of nucleosome positioning and its dynamic nature as well as the physical properties of chromatin.