-\subsubsection{Resetting the JABA services setting to their defaults}
-Once you have configured a JABAWS server and selected the OK button of the
-preferences menu, the settings will be stored in your Jalview preferences file,
-along with any preferences regarding the layout of the web services menu. If
-you should ever need to reset the JABAWS server list to its defaults, use the
-`Reset Services' button on the Web Services preferences panel.
-
-\subsection{Running your own JABA server}
-You can download and run JABA on your own machine using the `VMWare' or
-VirtualBox virtual machine environments. If you would like to learn how to do
-this, there are full instructions at the
-\href{http://www.compbio.dundee.ac.uk/jabaws/}{JABA web site}.
-
-\exercise{Installing a JABA Virtual Machine on your computer}{
-\label{jabawsvmex}{\sl This tutorial will demonstrate the simplest way of
-installing JABA on your computer, and configuring Jalview so it can access the JABA services.
-
-{\bf Prerequisites}
-
-You will need a copy of VMWare Player/Workstation/Fusion on your machine.
-}
-
-\exstep{If you do not have VMWare player installed, download it from
-www.vmware.com (this takes a few minutes -- you will need to register and wait
-for an email with a download link).}
-\exstep{Download the JABA virtual appliance archive called `jaba-vm.zip' from
-\textsf{http://www.compbio.dundee.ac.uk/jabaws/archive/jabaws-vm.zip}
-
-WARNING: This is large (about 300MB) and will take some time to download.
-}
-\exstep{Unpack the archive's contents to a place on your machine with at least
-2GB of free space.
-
-(On Windows, right click on the archive, and use the 'Extract archive..' option).
-}
-\exstep{Open the newly extracted directory and double click the VMWare virtual
-machine configuration file (jabaws.vcf). This will launch the VMWare player.
-}
-\exstep{Once VMWare player has started up, it may ask the question ``Did you move or copy
-this virtual appliance?'' -- select `Copy'.}
-\exstep{You may be prompted to download the VMWare linux tools. These are not
-necessary, so close the window or click on `Later'.}
-\exstep{You may also be prompted to install support for one or more devices (USB
-or otherwise). Say `No' to these options.}
-\exstep{Once the machine has loaded, it will display a series of IP addresses
-for the different services provided by the VM. Make a note of the JABAWS URL --
-this will begin with `http:' and end with `/jabaws''.}
-}
-
-\exercise{Configuring Jalview to access your new JABAWS virtual appliance}{
-\label{confnewjabawsappl}
-\exstep{Start Jalview (If you have not done so already).}
-\exstep{Enable the Jalview Java Console by selecting its option from the Tools
-menu.
-
-{\sl Alternately, use the System Java console if you have
-configured it to open when Jalview is launched, {\sl via} your system's Java
-preferences (under the `Advanced' tab on Windows).}}
-\exstep{Open the {\sl Preferences} dialog and locate the Web Services tab.}
-\exstep{Add the URL for the new JABAWS server you started in Exercise
-\ref{jabawsvmex} to the list of JABAWS urls using the `New Service
-URL' button.}
-\exstep{You will be asked if you want to test the service. Hit `Yes' to do this
--- you should then see some output in the console window.
-
-{\sl Take a close look at the output in the console. What do you think is
-happening?}
-}
-\exstep{Hit OK to save your preferences -- you have now added a new JABA
-service to Jalview!}
-\exstep{Try out your new JABA services by loading the ferredoxin sequences from
-http://www.jalview.org/tutorial/alignment.fa}
-\exstep{Launch an alignment using one
-of the JABA methods provided by your server. It will be listed under the JABAWS Alignment submenu of the {\sl Web Service} menu on the alignment window.
-
-{\sl Note: You can watch the JABA VM appliance's process working by opening the
-process monitor on your system. (On Windows XP, this involves right-clicking the
-system clock and opening the task manager -- then selecting the 'Processes' tab
-and sort by CPU).}
-}
-}
-
-\section{Multiple Sequence Alignment}
-\label{msaservices}
-Sequences can be aligned using a range of algorithms provided by JABA web
-services. These include ClustalW\footnote{{\sl ``CLUSTAL W: improving the
-sensitivity of progressive multiple sequence alignment through sequence
-weighting, position specific gap penalties and weight matrix choice."} Thompson
-JD, Higgins DG, Gibson TJ (1994) {\sl Nucleic Acids Research} {\bf 22},
-4673-80}, Muscle\footnote{{\sl ``MUSCLE: a multiple sequence alignment method
-with reduced time and space complexity"} Edgar, R.C.
-(2004) {\sl BMC Bioinformatics} {\bf 5}, 113}, MAFFT\footnote{{\sl ``MAFFT: a
-novel method for rapid multiple sequence alignment based on fast Fourier
-transform"} Katoh, K., Misawa, K., Kuma, K. and Miyata, T. (2002) {\sl Nucleic
-Acids Research} {\bf 30}, 3059-3066. and {\sl ``MAFFT version 5:
-improvement in accuracy of multiple sequence alignment"} Katoh, K., Kuma, K.,
-Toh, H. and Miyata, T. (2005) {\sl Nucleic Acids Research} {\bf 33}, 511-518.},
-ProbCons,\footnote{PROBCONS: Probabilistic Consistency-based Multiple Sequence
-Alignment.
-Do, C.B., Mahabhashyam, M.S.P., Brudno, M., and Batzoglou, S.
-(2005) {\sl Genome Research} {\bf 15} 330-340.} T-COFFEE\footnote{T-Coffee:
-A novel method for multiple sequence alignments. (2000) Notredame, Higgins and
-Heringa {\sl JMB} {\bf 302} 205-217} and Clustal Omega.\footnote{Fast, scalable
-generation of high-quality protein multiple sequence alignments using Clustal
-Omega. Sievers F, Wilm A, Dineen DG, Gibson TJ, Karplus K, Li W, Lopez R,
-McWilliam H, Remmert M, Soding J, Thompson JD, Higgins DG (2011) {\sl Molecular
-Systems Biology} {\bf 7} 539
-\href{http://dx.doi.org/10.1038/msb.2011.75}{doi:10.1038/msb.2011.75}} Of these,
-T-COFFEE is the slowest, but also the most accurate. ClustalW is historically
-the most widely used. Muscle is faster than ClustalW and probably the most
-accurate for smaller alignments and MAFFT is probably the best for large
-alignments, however Clustal Omega, which was released in 2011, is arguably the
-fastest and most accurate tool for protein multiple alignment.
-
-
-To run an alignment web service, select the appropriate method from the {\sl
-Web Service $\Rightarrow$ Alignment $\Rightarrow$ \ldots} submenu (Figure
-\ref{webservices}). For each service you may either perform an alignment with
-default settings, use one of the available presets, or customise the parameters
-with the `{\sl Edit and Run ..}' dialog box. Once the job is submitted, a
-progress window will appear giving information about the job and any errors that
-occur. After successful completion of the job, a new window is opened with the
-results, in this case an alignment. By default, the new alignment will be
-ordered in the same way as the input sequences; however, many alignment programs
-re-order the input to place homologous sequences close together. This ordering
-can be recovered using the `Original ordering' entry within the {\sl Calculate
-$\Rightarrow$ Sort } sub menu.
-
-\begin{figure}[htbp]
-\begin{center}
-\parbox[c]{1.5in}{\includegraphics[width=1.5in]{images/ws1.pdf}}
-\parbox[c]{2.5in}{\includegraphics[width=2.5in]{images/ws2.pdf}}
-\parbox[c]{2in}{\includegraphics[width=2in]{images/ws3.pdf}}
-\caption{{\bf Multiple alignment via web services} The appropriate method is
-selected from the menu (left), a status box appears (centre), and the results
-appear in a new window (right)}
-\label{webservices}
-\end{center}
-\end{figure}
-
-\subsubsection{Realignment}
-
-The re-alignment option is currently only supported by ClustalW and Clustal
-Omega. When performing a re-alignment, Jalview submits the current selection to
-the alignment service complete with any existing gaps. This approach is useful
-when one wishes to align additional sequences to an existing alignment without
-any further optimisation to the existing alignment. The Re-alignment service
-provided by ClustalW in this case is effectively a simple form of profile
-alignment.
-
-\subsubsection{Alignments of sequences that include hidden regions}
-
-If the view or selected region that is submitted for alignment contains hidden
-regions, then {\bf only the visible sequences will be submitted to the service}.
-Furthermore, each contiguous segment of sequences will be aligned independently
-(resulting in a number of alignment `subjobs' appearing in the status window).
-Finally, the results of each subjob will be concatenated with the hidden regions
-in the input data prior to their display in a new window. This approach ensures
-that 1) hidden column boundaries in the input data are preserved in the
-resulting alignment - in a similar fashion to the constraint that hidden columns
-place on alignment editing (see Section \ref{lockededits}), and 2) hidden
-columns can be used to preserve existing parts of an alignment whilst the
-visible parts are locally refined.
-
-\exercise{Multiple Sequence Alignment}{
-\exstep{ Close all windows and open the alignment at {\sf
-http://www.jalview.org/tutorial/unaligned.fa}. Select {\sl
-Web Service $\Rightarrow$ Alignment $\Rightarrow$ Muscle with Defaults}. A window will open giving the job status. After a short time, a second window will open with the results of the alignment.} \exstep{Select the first sequence set by clicking on the window and try running ClustalW and MAFFT (from the {\sl Web Service $\Rightarrow$ Alignment} menu) on the same initial alignment. Compare them and you should notice small differences. }
-\exstep{Select the last three sequences in the MAFFT alignment, and de-align them with {\sl Edit $\Rightarrow$ Remove All Gaps}. Press [ESC] to deselect them and then submit the view for re-alignment with ClustalW.}
-\exstep{Use [CTRL]-Z to recover the alignment of the last three sequences in the MAFFT alignment. Once the ClustalW re-alignment has completed, compare the results of re-alignment of the three sequences with their alignment in the original MAFFT result.}
-\exstep{Select columns 60 to 125 in the original MAFFT alignment and hide them. Select {\sl Web Services $\Rightarrow$ Alignment $\Rightarrow$ Mafft with Defaults} to submit the visible portion of the alignment to MAFFT. When the web service job pane appears, note that there are now two alignment job status panes shown in the window.}
-\exstep{When the MAFFT job has finished, compare the alignment of the N-terminal visible region in the result with the corresponding region of the original alignment. If you wish, select and hide a few more columns in the N-terminal region, and submit the alignment to the service again and explore the effect of local alignment on the non-homologous parts of the N-terminal region.}
-}
-
-
-\subsection{Customising the parameters used for alignment}
-
-JABA web services allow you to vary the parameters used when performing a
-bioinformatics analysis. For JABA alignment services, this means you are
-usually able to modify the following types of parameters:
-\begin{list}{$\bullet$}{}
-\item Amino acid or nucleotide substitution score matrix
-\item Gap opening and widening penalties
-\item Types of distance metric used to construct guide trees
-\item Number of rounds of re-alignment or alignment optimisation
-\end{list}
-
-
-\subsubsection{Getting help on the parameters for a service}
-Each parameter available for a method usually has a short description, which
-jalview will display as a tooltip, or as a text pane that can be opened under
-the parameter's controls. In the parameter shown in Figure
-\ref{clustalwparamdetail}, the description was opened by selecting the button on the left hand side. Online help for the
-service can also be accessed, by right clicking the button and selecting a URL
-from the pop-up menu that will open.
-
-\begin{figure}[htbp]
-\begin{center}
-\includegraphics[width=2.5in]{images/clustalwparamdetail.pdf}
-\caption{{\bf ClustalW parameter slider detail}. From the ClustalW {\sl Clustal $\Rightarrow$ Edit settings and run ...} dialog box. }
-\label{clustalwparamdetail}
-\end{center}
-\end{figure}
-
-\subsection{Alignment Presets}
-The different multiple alignment algorithms available from JABA vary greatly in
-the number of adjustable parameters, and it is often difficult to identify what
-are the best values for the sequences that you are trying to align. For these
-reasons, each JABA service may provide one or more presets -- which are
-pre-defined sets of parameters suited for particular types of alignment
-problem. For instance, the Muscle service provides the following presets:
-\begin{list}{$\bullet$}{}
-\item Huge
-\item Protein alignments (fastest speed)
-\item Nucleotide alignments (fastest speed)
-\end{list}
-
-The presets are displayed in the JABA web services submenu, and can also be
-accessed from the parameter editing dialog box, which is opened by selecting
-the `{\sl Edit settings and run ...}' option from the web serviceÔøΩs menu. If you have used
-a preset, then it will be mentioned at the beginning of the job status file shown
-in the web service job progress window.
-
-\subsubsection{Alignment Service Limits}
-Multiple alignment is a computationally intensive calculation. Some JABA server
-services and service presets only allow a certain number of sequences to be
-aligned. The precise number will depend on the server that you are using to
-perform the alignment. Should you try to submit more sequences than a service
-can handle, then an error message will be shown informing you of the maximum
-number allowed by the server.
-
-\subsection{User defined Presets}
-Jalview allows you to create your own presets for a particular service. To do
-this, select the `{\sl Edit settings and run ...}' option for your service,
-which will open a parameter editing dialog box like the one shown in Figure
-\ref{jwsparamsdialog}.
-
-The top row of this dialog allows you to browse the existing presets, and
-when editing a parameter set, allows you to change its nickname. As you
-adjust settings, buttons will appear at the top of the parameters dialog that
-allow you to Revert or Update the currently selected user preset with your changes, Delete the current preset, or Create a new preset, if none exists with the given name. In addition to the parameter set name, you can also provide a short
-description for the parameter set, which will be shown in the tooltip for the
-parameter set's entry in the web services menu.
-
-\begin{figure}[htbc]
-\center{
-\includegraphics[width=3in]{images/jvaliwsparamsbox.pdf}
-\caption{{\bf Jalview's JABA alignment service parameter editing dialog box}.}
-\label{jwsparamsdialog} }
-\end{figure}
-
-\subsubsection{Saving parameter sets}
-When creating a custom parameter set, you will be asked for a file name to save
-it. The location of the file is recorded in the Jalview user preferences in the
-same way as a custom alignment colourscheme, so when Jalview is launched again,
-it will show your custom preset amongst the options available for running the
-JABA service.
-
-%
-% \exercise{Creating and using user defined presets}{\label{createandusepreseex}
-% \exstep{Import the file at
-% \textsf{http://www.jalview.org/tutorial/fdx\_unaligned.fa} into jalview.}
-% \exstep{Use the `{\slDiscover Database Ids}' function to recover the PDB cross
-% references for the sequences.}
-% \exstep{Align the sequences using the default ClustalW parameters.}
-% \exstep{Use the `{\sl Edit and run..}'
-% option to open the ClustalW parameters dialog box, and create a new preset using
-% the following settings:
-% \begin{list}{$\bullet$}{}
-% \item BLOSUM matrix (unchanged)
-% \item Gap Opening and End Gap penalties = 0.05
-% \item Gap Extension and Separation penalties = 0.05
-% \end{list}
-%
-% As you edit the parameters, buttons will appear on the dialog box
-% allowing you revert your changes or save your settings as a new parameter
-% set.
-%
-% Before you save your settings, remeber to give them a meaningful name by editing
-% the text box at the top of the dialog box.
-% }
-% \exstep{Repeat the alignment using your new parameter set by selecting it from
-% the {\sl ClustalW Presets menu}.}
-% \exstep{These sequences have PDB structures associated with them, so it is
-% possible to compare the quality of the alignments.
-%
-% Use the {\sl View all {\bf N}
-% structures} option to calculate the superposition of 1fdn on 1fxd for both
-% alignments (refer to section \ref{superposestructs} for instructions). Which
-% alignment gives the best RMSD ? }
-% \exstep{Apply the same alignment parameter settings to the example alignment
-% (available from \textsf{http://www.jalview.org/examples/uniref50.fa}).
-%
-% Are there differences ? If not, why not ?
-% }
-% }
-
-\section{Protein alignment conservation analysis}
-\label{aacons}
-The {\sl Web Service $\Rightarrow$ Conservation} menu controls the computation
-of up to 17 different amino acid conservation measures for the current alignment
-view. The JABAWS AACon Alignment Conservation Calculation Service, which is used
-to calculate these scores, provides a variety of standard measures described by
-Valdar in 2002\footnote{Scoring residue conservation. Valdar (2002) {\sl
-Proteins: Structure, Function, and Genetics} {\bf 43} 227-241.} as well as an efficient implementation of the SMERFs
-score developed by Manning et al. in 2008.\footnote{SMERFS Score Manning et al. {\sl BMC
-Bioinformatics} 2008, {\bf 9} 51 \href{http://dx.doi.org/10.1186/1471-2105-9-51}{doi:10.1186/1471-2105-9-51}}
-
-\subsubsection{Enabling and disabling AACon calculations}
-When the AACon Calculation entry in the {\sl Web Services $\Rightarrow$
-Conservation} menu is ticked, AACon calculations will be performed every time
-the alignment is modified. Selecting the menu item will enable or disable
-automatic recalculation.
-
-\subsubsection{Configuring which AACon calculations are performed}
-The {\sl Web Services $\Rightarrow$ Conservation $\Rightarrow$ Change AACon
-Settings ...} menu entry will open a web services parameter dialog for the
-currently configured AACon server. Standard presets are provided for quick and
-more expensive conservation calculations, and parameters are also provided to
-change the way that SMERFS calculations are performed.
-AACon settings for an alignment are saved in Jalview projects along with the
-latest calculation results.
-
-\subsubsection{Changing the server used for AACon calculations}
-If you are working with alignments too large to analyse with the public JABAWS
-server, then you will most likely have already configured additional JABAWS
-servers. By default, Jalview will chose the first AACon service available from
-the list of JABAWS servers available. If available, you can switch to use
-another AACon service by selecting it from the {\sl Web Services $\Rightarrow$
-Conservation $\Rightarrow$ Switch Server} submenu.
-
-% TODO
-\section{Protein Secondary Structure Prediction}
-\label{protsspredservices}
-Protein secondary structure prediction is performed using the
-Jpred\footnote{{\sl ``The Jpred 3 Secondary Structure Prediction Server''} Cole, C., Barber, J. D. and Barton, G. J. (2008) {\sl Nucleic Acids Research} {\bf 36}, (Web Server Issue) W197-W201
-
-{\sl ``Jpred: A Consensus Secondary Structure Prediction Server''} Cuff, J. A.,
-Clamp, M. E., Siddiqui, A. S., Finlay, M. and Barton, G. J. (1998) {\sl
-Bioinformatics} {\bf 14}, 892-893} server at the University of
-Dundee\footnote{http://www.compbio.dundee.ac.uk/www-jpred/}. The behaviour of
-this calculation depends on the current selection:
-\begin{list}{$\circ$}{}
-\item If nothing is selected, Jalview will check the length of each alignment row to determine if the visible sequences in the view are aligned.
-\begin{list}{-}{}
- \item If all rows are the same length (often due to the
- application of the {\sl Edit $\Rightarrow$ Pad Gaps} option), then
- a JPred prediction will be run for the first sequence in the
- alignment, using the current alignment as the profile to use for prediction.
- \item Otherwise, just the first sequence will be submitted for a
- full JPred prediction.
-\end{list}
-\item If just one sequence (or a region in one sequence) has been selected, it
-will be submitted to the automatic JPred prediction server for homolog detection
-and prediction.
-\item If a set of sequences are selected, and they appear to be aligned using
-the same criteria as above, then the alignment will be used for a JPred
-prediction on the first sequence in the set (that is, the one that appears first in the alignment window).
-\end{list}
-Jpred is launched in the same way as the other web services. Select {\sl Web
-Services $\Rightarrow$ Secondary Structure Prediction $\Rightarrow$ JNet
-Secondary Structure Prediction}\footnote{JNet is the Neural Network based
-secondary structure prediction method that the JPred server uses.} from the
-alignment window menu (Figure \ref{jpred}).
-A status window opens to inform you of the progress of the job. Upon completion, a new alignment window opens and the Jpred
-predictions are included as annotations. Consult the Jpred documentation for
-information on interpreting these results.
-
-\begin{figure}[htbp]
-\begin{center}
-\includegraphics[width=2.25in]{images/jpred1.pdf}
-\includegraphics[width=3in]{images/jpred2.pdf}
-\caption{{\bf Secondary Structure Prediction} Status (left) and results (right) windows for JNet predictions. }
-\label{jpred}
-\end{center}
-\end{figure}
-
-\subsubsection{Hidden Columns and JNet Predictions}
-\label{hcoljnet}
-Hidden columns can be used to exclude parts of a sequence or profile from the
-input sent to the JNet service. For instance, if a sequence is known to include
-a large loop insertion, hiding that section prior to submitting the JNet
-prediction can produce different results. In some cases, these secondary structure predictions can be more reliable for sequence on either side of the insertion\footnote{This, of course, cannot be guaranteed.}. Prediction results returned from the service will
-be mapped back onto the visible parts of the sequence, to ensure a single frame
-of reference is maintained in your analysis.
-
-\exercise{Secondary Structure Prediction}{
-\label{secstrpredex}
-\exstep{ Open the alignment at \url{http://www.jalview.org/tutorial/alignment.fa}. Select the sequence {\sl FER\_MESCR} by clicking on the sequence ID. Then select {\sl Web Services $\Rightarrow$ Secondary Structure Prediction $\Rightarrow$ JNet Secondary Structure Prediction} from the alignment window menu. A status window will appear and after some time (about 2-4 min) a new window with the JPred prediction will appear. Note that the number of sequences in the results window is many more than in the original alignment as JNet performs a PSI-BLAST search to expand the prediction dataset.
-}
-% TODO: check how long this takes - about 2 mins once it gets on the cluster.
-\exstep{
-Select a different sequence and perform a JNet prediction in the same way. There will probably be minor differences in the predictions.
-}
-\exstep{
-Select the second sequence prediction, and copy and paste it into the first
-prediction window. You can now compare the two predictions. Jnet secondary structure prediction annotations are examples of {\bf sequence-associated alignment annotation}.
-% which is described in Section \ref{seqassocannot} below.
-}
-\exstep{
-Select and hide some columns in one of the profiles that were returned from the JNet service, and then submit the profile for prediction again.
-}
-\exstep{
-When you get the result, verify that the prediction has not been made for the
-hidden parts of the profile, and that the JPred reliability scores differ from the prediction made on the full profile.
-
-{\sl Note: you may want to keep this data for use in exercise \ref{viewannotfileex}.}
-}
-\exstep{
-In the original alignment that you loaded in step 1, {\bf select all} sequences,
-then open the {\bf Sequence ID $\Rightarrow$ Selection } submenu and select the
-{\bf Add Reference Annotation} option.