Lausanne Workshop
Goals of the meeting
The Lausanne workshop will take place on the 19th and 20th of March 2019. In this meeting, we will focus in drafting a proposal for restructuring of the Sequence Ontology regulatory subtree, and also lead a discussion regarding ways to go from experimental data to TF binding models and DBTF annotations.
- Philipp Bucher
18th of March:
Social activities:
- 19:00: Dinner.
19th of March:
Morning session:
- 08:45 – 10:45: Opening Symposium – session 1 (Room SV1717)
- 08:45 – 09:00: Opening (Philipp Bucher and Martin Kuiper).
- 09:00 – 09:35: Completing the collection of human TF motifs (Tim Hughes).
- 09:35 – 10:10: A flexible algorithm for fitting accurate biophysical models of protein-DNA interaction directly to SELEX data (Harmen Bussemaker).
- 10:10 – 10:45: A comprehensive Drosophila melanogaster transcription factor interactome (Sachi Inukai).
- 10:45 – 11:15: Coffee break.
- 11:15 – 13:00: Symposium – session 2 (Room SV1717)
- 11:15 – 11:50: Predicting regulatory interactions from transcription factor ChIP-seq data (Tim Bailey).
- 11:50 – 12:25: Fitting complementary motif sets to ChIP-seq data and dinucleotide weight tensors for TF specificities (Erik van Nimwegen).
- 12:25 – 13:00: Use of variability across individuals to identify gene regulatory elements (Judith Zaugg).
- 13:00 – 14:00: Lunch break.
Afternoon session:
- 14:00 – 15:45: Symposium – session 3 (Room SV1717)
- 14:00 – 14:35: From automated to curated annotation of regulatory elements and interactions in Ensembl (Daniel Zerbino).
- 14:35 – 15:10: Characterising mammalian regulatory elements in the light of evolution (Maša Roller).
- 15:10 – 15:45: Articulating the high throughput (epi)genomics data knowledge commons (Colin Logie).
- 15:45 – 16:15: Coffee break.
- 16:15 – 18:00: Break-out sessions:
- TF specificity models break-out 1 – Predicting the precise location of TF binding at regulatory DNA (Moderators: Philipp Bucher and Ivan Kulakovskiy) (Room SV17171):
- Part 1 (20 min): TFBS as a component of DNA-centric annotation: what is unclear. Ljubljana keypoints revisited.
- Part 2 (15 min): TFBS prediction and annotation: performance measures and descriptive quality criteria.
- Part 3 (10 min):(TFBS BE-IN 1) TFBS models open benchmarking initiative: current status (Ivan Kulakovskiy).
- Part 4 (30 min): (TFBS BE-IN 2) Benchmarking protocols: which are there and which are missing (Philipp Bucher).
- Part 5 (10 min): (TFBS BE-IN 3) Ensuring benchmarking re-usability by containerization of protocols (Ivan Kulakovskiy and Ilya Vorontsov).
- Part 6 (15 min): Proposed deliverables for DNA-centric annotation, and questions to DNA-centric group.
- DNA-centric annotation 1 – Regulatory elements for GREEKC (Moderators: Astrid Lægrid and Martin Kuiper) (Room AI153):
- Part 1 (15 min): How do regulatory elements fit in the main GREEKC use cases/cartoons?
- Part 2 (30 min): Review of available ontologies and proposed terms (GO/MSO/GRAO).
- Part 3 (45 min): Develop a short list of needed terms.
- Part 4 (15 min): Broad Yes/No proposals are voted upon and dissent is noted.
- TF specificity models break-out 1 – Predicting the precise location of TF binding at regulatory DNA (Moderators: Philipp Bucher and Ivan Kulakovskiy) (Room SV17171):
Social activities:
- 20:00: Dinner.
20th of March:
Morning session:
- 09:00 – 10:45: Break-out sessions:
- TF-specificity models break-out 2 -From the experimental data to TF binding models and TFBS annotations (Moderators: Vsevolod Makeev and Tim Hughes) (Room INR219):
- Part 1 (15 min): Introducing the table of DNA-protein interaction data (basing on //doi.org/10.1016/j.cell.2018.01.029). Possible additions after one year?
- Part 2 (10 min): (TFBS BE-IN 4) TF and data selection: the strategy and key sources of experimental data (Oriol Fornes, Skype).
- Part 3 (35 min): Motif discovery. Model selection depending on the availability of the experimental data. Can we formulate guidelines for prudent use of models of appropriate complexity?
- Part 4 (30 min):Motif finding / Pattern matching. TFBS occupancy as a function of site accessibility, TF concentration, and TF affinity. Competition between TF. What is to annotate?
- Part 5 (15 min): Which TFBS model and prediction descriptors should be included in TFBS prediction ontology?
- DNA-centric annotation 2 – Biochemical properties of regulatory elements. (Moderators: Judith Zaug, Maša Roller and Colin Logie) (Room DIA004).
- TF-specificity models break-out 2 -From the experimental data to TF binding models and TFBS annotations (Moderators: Vsevolod Makeev and Tim Hughes) (Room INR219):
- 10:45 – 11:00: Coffee break.
- 11:00 – 12:30: Joint session (Room INR219).
- 12:30 – 13:30: Lunch.
Afternoon session:
- 13:30 – 15:00: Break-out session:
- TF-specificity models break-out 3 (Moderators: Vsevolod Makeev and Anthony Mathelier) (Room INR219):
- Part 1 (45 min): (TFBS BE-IN 5) Roadmap: setting the stage for the open challenge (deadlines, key participants, invitation emails). Subtopics: standard representation of basic TFBS models (file formats, etc), and other technical questions.
- Part 2 (30 min): Lessons from joint sessions. TFBS annotation viewed as a part of DNA-centric annotation.
- Part 3 (15 min): Future plans + wrap-up for the final joint session.
- DNA-centric annotation 3 – Measurable properties of regulatory elements. (Moderators: Daniel Zerbino, Camille Berthelot and Tim Hughes) (Room DIA004):
- Part 1 (45 min): What are the measurable properties of a regulatory element, and what assays are available to measure them?
- Part 2 (30 min): What are the existing data sets? Which data types are linked to which WG1 terms defined in this workshop?
- Part 3 (15 min): Data sets to benchmark the GRAO.
- TF-specificity models break-out 3 (Moderators: Vsevolod Makeev and Anthony Mathelier) (Room INR219):
- 15:00 – 15:15: Coffee break.
- 15:15 – 17:00: Wrap-up session, action points (Room INR219).
Social activities:
- 19:00: Dinner.
Summary Results
A TFBS Benchmarking initiative was launched, resulting in PMID: 32393327
A new structure for the SO regulatory subtree was proposed:
-
- Chromosomal Region (see SO for the exact term):
- Regulatory Region
- Is_a: Promoter
- (has part)Part: Core Promoter
- Is_a: Core Eukaryotic Promoter
- Part: Transcription Start Site
- Part: Transcription Factor Binding Site
- Is_a: Eukaryotic Promoter
- Part: Core Eukaryotic Promoter
- Part: Eukaryotic Transcription Start Site
- Part: BS for Eukaryotic General (Basal) Transcription Factors
- Is_a: Bacterial Promoter
- Is_a: Viral Promoter
- (has part)Part: Core Promoter
- Is_a: Enhancer
- Is_a: Promoter
- Regulatory Region
- Chromosomal Region (see SO for the exact term):
- Part: Transcription Factor Binding Site
-
-
- Is_a: Silencer
- Part: Transcription Factor Binding Site
- Is_a: Insulator
- Part: Transcription Factor Binding Site
- Is_a: Anchor
- Part: Transcription Factor Binding Site
- Is_a: TAD Boundary
- Part: Transcription Factor Binding Site
- Is_a: Silencer
-
Is_a: Transcription Factor Binding Site
- Is_a: DNA Loop
- Necessary Part: Anchor
- Is_a: Chromatin Regulatory Region
- Epigenetic … (nucleosome modification, covalent post-replicational DNA modification)
- Is_a: Topologically Associated Domain (TAD)
- Necessary Part: TAD Boundary