====== HMMER ======
This tutorial follows the HMMER User’s Guide written by Sean R. Eddy, Travis J. Wheeler and the HMMER development team. Thanks.
===== Problem 1 - Install HMMER =====
First of all, we download HMMERv3.1b2 from http://hmmer.org and unpack it.
<code|bash>
wget http://eddylab.org/software/hmmer3/3.1b2/hmmer-3.1b2.tar.gz
tar xfv hmmer-3.1b2.tar.gz
cd hmmer-3.1b2
</code>
Now we have downloaded the HMMER source code. Now, it's time to compile it.
<code|bash>
./configure
make
make check
</code>
Probably, we don't have root privileges so add binaries to the PATH variable.
<code|bash>
export PATH=/path/to/hmmer-3.1b2/src:$PATH
</code>

===== The programs in HMMER =====
- Build models and align sequences (DNA or protein)
	- hmmbuild - Build a profile HMM from an input multiple alignment.
	- hmmalign - Make a multiple alignment of many sequences to a common profile HMM
- Search protein queries against protein database
	- phmmer - Search a single protein sequence against a protein sequence database. (BLASTP-like)
	- jackhmmer - Iteratively search a protein sequence against a protein sequence database. (PSIBLAST-like)
	- hmmsearch - Search a protein profile HMM against a protein sequence database.
	- hmmscan - Search a protein sequence against a protein profile HMM database.
	- hmmpgmd - Search daemon used for hmmer.org website.

And many others....


=====Searching a protein sequence database with a single protein profile HMM=====
===Step 1: build a profile HMM with hmmbuild===
Common use of HMMER is to search a sequence database for a protein family of interest (homologues).

Look at the file ''tutorial/globins4.sto''
<note tip>What can you see there?</note>

Construct a HMM from an alignment
<code|bash>
hmmbuild globins4.hmm tutorial/globins4.sto
</code>
Look at the globins4.hmm. Is it what you expected?
Now, you have a sequence database to search.


===Step 2: search the sequence database with hmmsearch===
Run your example search against tutorial/globins45.fa.
<code|bash>
hmmsearch globins4.hmm tutorial/globins45.fa > globins4.out
</code>
<note important>Discuss the results!</note>

====Single sequence protein queries using phmmer====
As BLASTP or FASTA, the phmmer is for searching a single sequence query against a sequence database.

<code|bash>
phmmer tutorial/HBB_HUMAN tutorial/globins45.fa > phmmer.out
</code>
Everything about the output is essentially as for hmmsearch .


====Searching a profile HMM database with a query sequence====
The HMM database can be Pfam, SMART, or TIGRFams, or another database of your choice.

===Step 1: create an HMM database flatfile===
A flatfile is just a concatenation of individual HMM files. Given this, we firstly build individual hmm files using ''hmmbuild'' and concatenate them using ''cat''.
Let's create a small database from the files of tutorial dir.
<code|bash>
hmmbuild globins4.hmm tutorial/globins4.sto
hmmbuild fn3.hmm tutorial/fn3.sto
hmmbuild Pkinase.hmm tutorial/Pkinase.sto
cat globins4.hmm fn3.hmm Pkinase.hmm > minifam
</code>
In this case, the minifan is our new hmm database. Because of accelaration, compress and index the flatfile with hmmpress.
<code|bash>
hmmpress minifam
</code>
See new four binary files in the dir.

===Step2: search the HMM database with hmmscan===
Now we can analyze sequences using our HMM database and ''hmmscan''.
<code|bash>
hmmscan minifam tutorial/7LESS_DROME
</code>

====TASK 1: find records in Pfam database ====
In the previous example, we used three records in the stockhold format: ''globins4.sto'', ''fn3.sto'', and ''Pkinase.sto''. However, What can we do wheather we do not have any source records? 

<note tip>Which database to use?</note>

Your task is following:
  - Choose a profile HMMs database.
  - Find three protein families: ''globin'', ''fn3'', and ''Pkinase''. Download their alignments  as a seed file (contains representative members of the family which are judged to be well aligned) in the stockholm format.
  - Construct the HMM database (see the previous example).
  - Analyse ''tutorial/7LESS_DROME'' using our HMM database.