From 1ebd3509c68140dce2759e97c8b02d0f8713fa14 Mon Sep 17 00:00:00 2001
From: Marc Gouw <marc.r.gouw@gmail.com>
Date: Wed, 9 Nov 2016 13:39:50 +0100
Subject: [PATCH] Added ELM material.
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TeachingMaterials/elm.md | 114 +++++++++++++++++++++++++++++++++++++++
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- [TMHMM](http://www.cbs.dtu.dk/services/TMHMM/)
- [IUPRED](http://iupred.enzim.hu/) and [Anchor](http://anchor.enzim.hu/)
5. Intrinsically disordered region: Marc
- - ELM
+ - [ELM](https://git.embl.de/sharan/protein-bioinformatics-nov-2016/blob/master/TeachingMaterials/elm.md)
- [DisProt](https://git.embl.de/sharan/protein-bioinformatics-nov-2016/blob/master/TeachingMaterials/disprot.md)
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+# Short Linear Motifs
+
+This text was largely adapted from a [tutorial written by Holger
+Dinkel][elm_tutorial] for the [EMBO Practical Course on computational analysis
+of protein-protein interactions][embo_course_ppi]
+
+[elm_tutorial]: http://aidanbudd.github.io/course_EMBO_at_TGAC_PPI_Sep2015/trainingMaterial/holgerDinkel/linear_motifs/
+[embo_course_ppi]: http://aidanbudd.github.io/course_EMBO_at_TGAC_PPI_Sep2015//
+
+## Eukaryotic Linear Motifs
+
+Eukaryotic Linear Motifs (or ELMS) sometimes also known as short Linear Motifs
+(SLiMs) are short sequences typically found in disordered regions that have
+important roles in the function of a protein.
+
+## The ELM database
+
+The [ELM database][elm] is a project who's ultimate goal it is to all occurences
+of ELMs and their function in all known proteins(!).
+
+It consists of manually annotated entries carefully curated by experts in a
+particular field, working in a certain protein, or a particular motif. These
+annotators are responsible for contributing ELM **classes**, which represent
+linear motifs with a known function, and experimentally verified **instances**
+of this motif.
+
+- **types** There are 6 types of motifs: LIG: ligand binding, MOD:
+ modification, TRG: targeting, DOC: docking, DEG: degradation, CLV: cleavage.
+
+- **class** is a sequence of amino acids with a given function, based on
+ binding partner, modifying enzyme, acting peptidase and targeted subcellular
+ localisation. Each **class** is defined by a **regular expression**
+
+- **instance** an manually annotated occurrence of a **class** in a protein,
+ verified by a literature citable experiment.
+
+[elm]: http://elm.eu.org
+
+## Browsing content
+
+## Exercise 1: Browsing content
+
+There are two main ways in which the ELM database content can be browsed.
+
+Click on "ELM DB" -> "ELM Classes", or follow the link to the ELM classes page:
+http://elm.eu.org/elms to browse the ELM **classes** that have been annotated.
+
+Use the search (or side filters) to find the ELM motif: **DOC_CYCLIN_1**
+
+- **Question 1:** What does this motif do?
+- **Question 2:** How many instances are annotated in the database?
+- **Question 3:** Which Gene Ontology terms is this motif associated with?
+
+This motif was identified in P53 in the sequence: **KKLMF**
+
+- **Question 4:** What is the starting and finishing position of this sequence
+ in P53?
+- **Question 5:** Which experimental protocols were used to infer the existence
+ of this instance?
+- **Question 6:** How certain are we about this annotation?
+- **Question 7:** What activates P53 in the pathway to induce apoptosis?
+
+## Exercise 2: The ELM Prediction tool
+
+Navigate to the "ELM predictions" page.
+
+Search protein **SRC_HUMAN** (accession P12931) for ELMs using the following parameters:
+
+- Cell Compartment: Not specified
+- Motif Probability Cutoff: 100
+- Context information: (leave blank)
+
+- **Question 1:** How many instances do you find?
+- **Question 2:** What can you say about the globularity of the protein? Does
+ it have globular and/or disordered regions?
+
+Redo the above search, this time using the following parameters:
+
+- Cell Compartment: cytosol
+- Motif Probability Cutoff: 0.01
+- Context information: Homo sapiens
+
+- **Question 3:** How many instances do you find now?
+- **Question 4:** How many of the instances are manually annotated?
+- **Question 5:** Do the structural predictors/filters (SMART, GlobPlot,
+ IUPRED, Secondary Structure) agree in terms of which regions are
+structured/disordered?
+- **Question 6:** Compare the location of the annotated instances with
+ structural information at hand (IUPRED, Secondary Structure).
+- **Question 7:** How many deteced instances were removed by the
+ SMART/Structure filter?
+- **Question 8:** For the annotated instances, which of the ELM classes require
+ a phosphorylation at a certain residue of the motif? (Hint: This information
+can be found in the description of the ELM class)
+- **Question 9:** Which residue in SRC_HUMAN corresponds to this and can you
+ find evidence for a phosphorylation of this residue (using Phospho.ELM)?
+
+
+## Exercise 3: The ELM Prediction tool
+
+Search ELM using the protein name **MDM4_HUMAN** and look for the ‘USP binding motif’ **DOC_USP7_MATH_1**
+
+- **Question 1:** How many such motif instances are found in this protein sequence?
+- **Question 2:** How many of these have been exprimentally validated (i.e., are manually annotated?), and what are the "FP" annotations?
+
+## Exercise 4: Switches
+
+Use the ELM "global search box" (on the top right) to search for the class
+**LIG_SH3_2**. (Just start typing, and wait for the autocomplete to finish).
+
+Click on "LIG_SH3_2" to visit the class page.
+
+- **Question 1:** How many switches are annotated for this class?
+- **Question 2:** What is the mechanism that results in the switching event in **SYNJ2_RAT**?
--
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