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== General information ==

=== Where and when ===
Lectures plus subsequent exercises will take place every Tuesday afternoon during the semester, starting '''Tuesday Feb 2 at 13:00'''.

'''In 2021, the course will be held online during the entire semester.'''


For online lectures and exercises, we use Microsoft Teams.  The code for joining this year's team is:
tvii8l9
Please see the '''[[MS Teams instructions]]!'''


=== Teachers ===

* [http://www.dtu.dk/service/telefonbog/person?id=25617&cpid=257116&tab=2&qt=dtupublicationquery Henrik Nielsen] — Associate professor, course responsible.
* [https://www.dtu.dk/service/telefonbog/person?id=18103&tab=2&qt=dtupublicationquery Rasmus Wernersson] — External associate professor, course responsible.
* [http://www.dtu.dk/service/telefonbog/person?id=34983&tab=2&qt=dtupublicationquery Paolo Marcatili] — Associate professor, guest lecturer. Topic: Protein structure.
* [http://www.dtu.dk/service/telefonbog/person?id=5118&tab=2&qt=dtupublicationquery Anders Gorm Pedersen] — Professor, guest lecturer. Topic: Phylogenetic trees.


=== Teaching assistants ===
* [https://www.dtu.dk/service/telefonbog/person?id=149708 Amelie Fritz] — PhD student
* [https://www.dtu.dk/service/telefonbog/person?id=140521 Anna-Lisa Schaap-Johansen] — PhD student
* [https://www.dtu.dk/service/telefonbog/Person?id=158424 Klara Marie Andersen] — PhD student
* [https://www.dtu.dk/service/telefonbog/Person?id=97554 Marianne Helenius] — PhD student
* [https://www.inside.dtu.dk/en/dtuinside/generelt/telefonbog/person?id=144521 Morgane Chauvet] — MSc student


=== Course content ===
In this course, a large emphasis is placed on the practical usage of bioinformatics databases and tools. A typical lecture will present the theoretical aspects of the topics of the day — sometimes including a small group exercise using pen and paper — and last about an hour. The rest of the time will be spent on practical computer exercises, where the teachers and teaching assistants will be ready to help.

See also [http://kurser.dtu.dk/course/22111 the course base about 22111].

=== Curriculum ===
There is no formal textbook. The curriculum consists of the exercise guides, supplemented with various papers and chapters which will be made available on this homepage or on DTU Learn. Please note that ''all'' exercise guides are mandatory curriculum — including the ''answers'' to the exercises which will be made available on DTU Learn after each exercise.

=== Computers ===
====Hardware====
'''You must bring your own laptop''' to the exercises, and it must be able to connect to DTU's wireless network. The type of computer / operating system is not important; Windows, Mac or Linux will all work fine. An iPad or an Android tablet, on the other hand, will not be good enough. A Chromebook will also not be enough (unless you have succeeded in installing a Linux distribution on it, but in that case we assume you know what you're doing).

In some of the exercises ("PDB/PyMOL", "Malaria vaccine", and "Old exam questions"), you will work with the molecular visualization program PyMOL. This is rather difficult to control by a touchpad, so please remember to '''bring a mouse'''. The mouse should have two buttons plus a scroll-wheel.

====Software====
# Most importantly: an updated '''internet browser''' (e.g. [http://www.google.com/chrome Google Chrome], [http://www.mozilla.com/ FireFox], [http://www.opera.com/ Opera], [https://www.microsoft.com/edge Edge] for Windows or Mac OS, or Safari for Mac only). '''NB:''' You must have more than one browser installed; Safari for Mac or Edge for Windows may have glitches with some bioinformatics websites, and in those cases it is important to be able to switch to an alternative browser.
# '''Java''' runtime engine is needed for running some of the software we use in the course, including jEdit (see below). Download from here: https://adoptopenjdk.net/ - choose OpenJDK 11 and HotSpot.
#* '''NOTE:''' Oracle java 8 from https://java.com/en/ is NOT good enough for jEdit anymore. jEdit version 5.6 and later needs java 11 which is available from the above link (and from a few other places). AdoptOpenJDK is open source and free, even for commercial use, which is not the case for Oracle java anymore.
#* '''IMPORTANT TIP''' for Windows users: You need to enable the sub-feature named "set JAVA_HOME variable" when installing java 11.
# A plain text editor for working with, e.g., sequence files. We recommend '''jEdit''', which you can download for free from http://www.jedit.org. If you experience unsolvable problems installing or running jEdit, there are alternatives, e.g. [http://geany.org/ Geany].
#* '''NOTE:''' The jEdit developers have not signed the installation package, therefore both Windows and MacOS will complain when you first attempt to install it, and you have to insist that it is OK to run the program. For Macs, this is a bit complicated, see the instructions in [[ExJEdit#Download_and_Install_jEdit|the exercise guide]].
Other software will be installed during the exercises.

=== Hand-ins ===
As preparation for the computer-based exam, each participant or group must write a "'''logbook'''" with answers to the questions posed in the exercise guides. After the exercise, you should upload the logbook to DTU Learn.


You decide which software you prefer for writing the logbook — e.g. Microsoft Word, [http://www.libreoffice.org/ LibreOffice] (free), [http://www.openoffice.org/ Apache OpenOffice] (free), Pages for Mac, [https://docs.google.com/ Google Docs] or similar. You should be able to insert '''screenshots''' in the logbooks for documentation purposes. Microsoft Word has a built-in screenshot tool. Both Windows 10 and Mac OS also have dedicated screenshot tools.


Regardless of your choice of writing software, the result '''must be handed in as a PDF file'''. LibreOffice and Google Docs can make PDFs directly. MacOS and Windows 10 have built-in functions for converting any printable file to PDF. Users of earlier versions of Windows must install a separate program. Several free alternatives exist, e.g. [http://www.primopdf.com/ PrimoPDF]. (It can be a good idea to install PrimoPDF even for Windows 10 users, it provides some extra options and the resulting files take up less space).

'''Please do ''not'' copy the questions''' from the exercise guide to your logbook. The hand-in module on DTU Learn has a system for plagiarism detection, which will raise an alarm if significant portions of your hand-in are identical to documents found on the internet — and that includes the exercise guides.

'''NB:''' ''The hand-ins do not affect your grade'' — they are mainly meant as a preparation for the exam. They are also a means for us to check the understanding of the teaching; if we can see that many participants have made the same mistake, we will try to explain the issue better at the next lecture.

=== Exam ===
The 22111 exam is electronic; i.e. you must bring your own computer, and you will ''not'' get a paper copy of the questions. The questions will be made available as a PDF file on the DTU online exam system.  The only accepted hand-in format is PDF.

All aids are allowed at the exam; you can bring any books, papers or notes. You will have '''open access to the internet''' which includes all the materials and websites we have used during the course. You are also allowed to search information on Google, Wikipedia, etc., but you are ''not'' allowed to communicate with others through e-mail, Facebook, chat, or file sharing websites. The internet traffic will be logged during the exam to ensure that these restrictions are kept.

Just like in the weekly hand-ins, we kindly ask you: ''Please don't copy the questions in your answer document'' — that might result in the answer being flagged as plagiarism.


=== DTU Learn & Inside ===
Link to this year's DTU Learn page: https://learn.inside.dtu.dk/d2l/home/60286

Link to this year's DTU Inside group: https://cn.inside.dtu.dk/cnnet/element/633911/

=== Evaluation and feedback ===
We will be very happy to receive comments, suggestions, criticisms, or praise at any time during the semester. You can:
* send them by email to the teachers, or
* write them under "General feedback" in "Discussion" in the DTU Inside group (found in the Course content menu), or
* write them in the "General" channel in MS Teams.
If somebody writes a message in the "Discussion" or "General" channel, you can comment on it. If you see a message you agree on, please comment "Agree!" so that we can see that it is not just one person's opinion.

In addition, we will conduct a mid-term evaluation in [https://evaluering.dtu.dk/ DTU evaluation].

== Lecture & exercise plan ==

Note: This is a ''preliminary'' plan, changes may occur!

=== Tuesday Feb 2 — Introduction & taxonomy ===
:'''Lectures:'''
:* ''Introduction to the course, bioinformatics, and computers'' — Henrik Nielsen.
:* ''Evolution and taxonomy'' — Rasmus Wernersson.
:'''Slides:''' will be made available on DTU Learn.
:'''Curriculum:''' [http://www.cbs.dtu.dk/dtucourse/27611spring2011/PDF/Chapter2_Evolution.pdf Brief Introduction to Evolutionary Theory] — Written by Anders Gorm Pedersen.
:'''Test of prior knowledge:''' Go to https://evaluering.dtu.dk/, click "Test of prior knowledge" under 22111, and fill out the form (it's anonymous). Spend max. 10 minutes on it.
:'''Exercises:'''
:# [[Plain text files and jEdit]] 
:# [[Taxonomy databases]] 
:'''Extra material'''
:*"[[Media:ELS_bioinformatics.pdf|Bioinformatics]]" — Encyclopedia entry from 2009.
:*"[https://academic.oup.com/nar/article/49/D1/D10/5937080 Database resources of the National Center for Biotechnology Information]" — article from the annual database issue of Nucleic Acids Research, 2021.

=== Tuesday Feb 9 — GenBank ===
:'''Lecture:''' ''DNA as Biological Information'' — Rasmus Wernersson
:'''Curriculum:''' [[Media:DNA_SequencingTutorial.pdf|DNA sequencing tutorial]] — source: IDT Tech Vault
:'''Handout''' for the lecture: [[Media:HandoutEx_BaseCalling_Simple.pdf‎|"Base-calling" exercise (for printing)]] [PDF] / [[Media:BaseCalling_on_screen_version.pdf|"Base-calling" exercise (version for on-screen viewing)]] [PDF].
:'''Slides:''' on DTU Learn.


:'''Exercise:''' [[ExGenbank-new|Using the GenBank database]] — ([[ExGenbank-new-answers|Answers]])
:'''Reference material''' for the exercise: [[Media:GenBank+FASTA_handout_revised.pdf|GenBank + FASTA format]] [PDF]

:'''Background material''' (supposedly known):
:*[[File:Phone_34.gif‎]] [http://www.youtube.com/watch?v=YgmoHtLGb5c mRNA splicing] (YouTube).
:*[[Media:GeneStructure.pdf|Overview of eukaryotic gene structure]] (PDF).

:'''Extra material:'''
:*[http://www.ncbi.nlm.nih.gov/books/NBK44863/ Entrez Sequences Quick Start] (NCBI)
:*[https://academic.oup.com/nar/article/49/D1/D92/5983623 "GenBank"] — article from the annual database issue of Nucleic Acids Research, 2021.

=== Tuesday Feb 16 — Translation & UniProt ===
:'''Lecture:''' ''Protein databases'' — Henrik Nielsen
:'''Curriculum:''' [[Media:VirtualRibosome.pdf|Virtual Ribosome]] — software article (PDF).
:'''Slides:''' on DTU Learn.

:'''Exercises:'''
:#[[Exercise: Translation - Virtual Ribosome]] — ([[ExTranslation-answers|Answers]])
:#[[Exercise: The protein database UniProt]] — ([[ExUniProt-answers|Answers]])
:'''Background material''' (supposedly known):
:*[http://www.cbs.dtu.dk/dtucourse/27611spring2011/PDF/protein_handout.pdf Levels of protein structure] [PDF]
:*[[Media:GeneStructure.pdf|Overview of eukaryotic gene structure]] (PDF).

:'''Extra material:'''
:*[https://academic.oup.com/nar/article/49/D1/D480/6006196 "UniProt: the universal protein knowledgebase in 2021"] — article from the annual database issue of Nucleic Acids Research, 2021.
:*[[Media:uniprotkb_quickguide.pdf|"A Quick Guide to UniProtKB"]] — nice printable overview.

=== Tuesday Feb 23 — Pairwise alignment ===
:'''Lecture:''' ''Pairwise alignment'' — Henrik Nielsen.
:'''Curriculum:''' Page 35-55 in Immunological Bioinformatics (PDF: on DTU Learn → General information and files → Textbook excerpt).
:'''Handout''' for the lecture: [[Media:New_handout_alignscores.pdf|Alignment scores]]
:'''Slides:''' on DTU Learn.
:'''Exercise:''' [[ExPairwiseAlignment|Pairwise alignment]] 


=== Tuesday Mar 2 — Protein structure, PDB & PyMOL ===
:'''Remember to bring a mouse for this day's exercise.''' The mouse should have two buttons and a scroll wheel.
:'''Lecture:''' ''Protein 3D structure'' — Paolo Marcatili
:'''Curriculum:''' [http://en.wikipedia.org/wiki/Protein_structure Protein Structure (Wikipedia)]
:'''Slides:''' on DTU Learn.

:'''Link to advanced course:'''
::* [http://teaching.healthtech.dtu.dk/36617/index.php/22117_-_Protein_Structure_and_Computational_Biology 22117 Protein Structure and Computational Biology]

:'''Software''' for installation: [https://pymol.org/2/ PyMOL]
::'''Note:''' you will need the license file found at DTU Learn under this week's topic.
:'''Exercises:'''
:#[[Media:PyMol_tutorial2017_v4.pdf|PyMol tutorial]] (PDF) — basic usage of PyMOL.
:#[[Protein Structure and Visualization]] — ([[Protein_Structure_and_Visualization_Answers|Answers]]; NB: the last section labelled "PyMOL magic" is NOT curriculum, just a tip!)

:'''Extra material:'''
:*[https://academic.oup.com/nar/article/49/D1/D437/5992282 "RCSB Protein Data Bank: powerful new tools for exploring 3D structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences"] — article from the annual database issue of Nucleic Acids Research, 2021.
:*[[PyMOL]] — some tips and tricks.
:*[http://www.cbs.dtu.dk/~blicher/Courses/PyMOL_structure_navigation.pdf PyMOL basics — a small example] (optional extra exercise)

=== Tuesday Mar 9 — BLAST ===
:'''Lecture:''' ''Introduction to BLAST'' — Rasmus Wernersson.
:'''Curriculum:''' section 3.2.5 → 3.3 (i.e. pages 47-52) in Immunological Bioinformatics (PDF: on DTU Learn).
:'''Slides:''' on DTU Learn.
:'''[[Exercise: BLAST]]''' 
:'''Extra material:'''

::[[File:Phone_34.gif‎]] '''Videos about BLAST from NCBI:''' (Video introduction to NCBI's web interface and Expect Values) [http://www.youtube.com/playlist?list=PLH-TjWpFfWrtjzMCIvUe-YbrlIeFQlKMq NCBI's YouTube channel]

=== Tuesday Mar 16 — Case: Malaria vaccine ===
:'''Lecture:''' ''Malaria and vaccines'' — [https://cmp.ku.dk/staff/?pure=en/persons/226923 Thomas Lavstsen], Associate Professor, University of Copenhagen
:'''Curriculum:''' [http://www.cdc.gov/dpdx/malaria/ Malaria — Causal Agents / Life Cycle]
:'''Slides:''' on DTU Learn.
:'''Exercise:''' [[Exercise:Malaria Vaccine|Malaria vaccine]] 

=== Tuesday Mar 23 — Sequence information & logo-plots ===
:'''Lecture:''' ''Sequence information & logo-plots'' — Henrik Nielsen
:'''Curriculum:'''
:# Pages 68-80 in Immunological Bioinformatics (PDF: on DTU Learn).
:# Pages 1-8 of "''Information theory primer''" ([http://www.cbs.dtu.dk/courses/27040/teachingmaterials/informationtheory_primer.pdf PDF])
:#* Read also the appendix on logarithms (especially Log<sub>2</sub>) if needed!
:'''Slides:''' on DTU Learn.
:'''Handout''' for the lecture: [[Media:logo_exercise.pdf|How to construct sequence logos]] (PDF)
:[[Image:Emblem-important_tiny.png‎]] '''Mid-term evaluation:''' Go to https://evaluering.dtu.dk/ and click "Mid-term evaluation" under 22111 [[Image:Emblem-important_tiny.png‎]]
:'''Exercise:''' [[ExSeqLogos|DNA and Peptide Logos]] 

------
<div align="center">
[[Image:Easter-egg-free-to-use-cliparts.png|25px]] '''Easter holidays''' [[Image:Easter-egg-free-to-use-cliparts.png|25px]]
</div>
------

=== Tuesday Apr 6 — Weight matrices and other prediction methods ===
:'''Lecture:''' ''Introduction to prediction methods, especially Weight Matrices'' — Henrik Nielsen
:'''Curriculum:''' Same as last week!
:'''Slides:''' on DTU Learn.
:'''Handouts''' for the lecture: [[Media:Estimationofpseudocounts_new+examples.pdf|How to estimate pseudo frequencies]]  
:'''Exercise:''' [[Exercise: Construction of sequence logos and weight matrices|Construction of weight matrices]] 
:'''Link to advanced course: '''
:: [http://teaching.healthtech.dtu.dk/22125/ 22125: Algorithms in bioinformatics]

=== Tuesday Apr 13 — PSI-BLAST ===
:'''Lecture:''' ''PSI-BLAST'' — Rasmus Wernersson
:'''Curriculum:'''
:'''Slides:''' on DTU Learn.
:'''Exercise:''' [[ExPSIBLAST|PSI-BLAST]] 

=== Tuesday Apr 20 — Multiple alignments ===
:'''Lecture:''' ''Multiple alignment'' — Henrik Nielsen
:'''Curriculum:''' RevTrans ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC169015/ article])
:'''Slides:''' on DTU Learn.
:'''Exercise:''' [[Exercise: Multiple Alignments (English version)|Multiple Alignments]] 


=== Tuesday Apr 27 — Phylogenetic trees ===
:'''Lecture:''' ''Phylogenetic Reconstruction: Distance Matrix Methods'' — Anders Gorm Pedersen
:'''Curriculum:'''
:# ''Introduction to Tree Building'', PDF on Learn 
:# ''[http://evolution.berkeley.edu/evolibrary/article/phylogenetics_01 Evolutionary trees]'' (minus the section "How to reconstruct an evolutionary tree")
:# ''Understanding Evolutionary Trees'', [http://www.cbs.dtu.dk/courses/27615/pdf/understanding_evo_trees.pdf PDF].
:'''Slides:''' on DTU Learn.
:'''Handout''' for lecture: [http://www.cbs.dtu.dk/dtucourse/27611spring2008/Ex09_Phylo/handout_distance.pdf Reconstructing a distance tree] 
:'''Software''' for installation: [http://tree.bio.ed.ac.uk/software/figtree/ FigTree tree-viewer]
::'''IMPORTANT NOTE''' for Windows users: Download the <tt>.zip</tt> file and unpack it. Then, go to the "lib" subfolder and double-click the <tt>.jar</tt> file. The <tt>.exe</tt> file will not work.
:'''[[Exercise: Phylogeny]]''' 
:'''Link to advanced course:'''
::* [http://teaching.healthtech.dtu.dk/22115/ 22115 Computational Molecular Evolution]

=== Tuesday May 4 — Bioinformatics in practice + old exam questions ===
:'''Lecture:''' "Real life case": ''Bioinformatics and Systems Biology in precision medicine'' - Rasmus Wernersson
:'''Curriculum:''' (None - lean back and enjoy)
:'''Slides:''' on DTU Learn.
:'''Exercise:''' We train on the old exam set from '''2020''' - available on DTU Learn.

== Exam ==

=== Wednesday May 26 ===
'''Summer exam 2021:''' Go to https://eksamen.dtu.dk/ and find 22111.

[[Media:Vejledning_til_studerende_DE_Digital_Eksamen_DK-UK.pdf|Here is a guide]] to the Digital Exam interface (in Danish and English).

The assignment will be accessible from '''XX:XX''' on Wednesday May 26.

=== Checklist for computers ===
Check here whether your computer has all the software needed for the exam: [[Checklist for computers]]

=== Link collection ===
A quick overview of the websites we have used in the course: [[Link collection]]

=== FAQ ===
Questions we have received and answered: [[FAQ]]

22111:Course plan spring 2021 - Revision history