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<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN">
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<title>NetControl4BioMed: Documentation</title>
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<header>
<h1>Documentation for NetControl4BioMed</h1>
<a href="documentation.html" target="_new">Documentation</a>
<a href="download.html" target="_new">Download</a>
<a href="http://combio.abo.fi/research/network-controlability-project/" target="_new">The Project Page</a>
<a href="about.html" onclick="window.open('about.html', 'newwindow', 'width=700, height=520'); return false;">About</a>
<a href=".">Home</a>
</header>
<div class=\"main-content\" style="width: 1600px; margin:10 auto; background-color: white; ">
<h2>Pipeline</h2>
<p style="margin-top: 0pt;">The pipeline generates a biochemical network basing on the user's query,
and searches for a smallest combination of driven nodes via which one should be able to control a user-selcted set of target nodes there.</p>
<p style="margin-top: 0pt;"> <b>The pipeline
consists of the following three parts:</b> </p>
<ol>
<li> <b>DATA IMPORT:</b> Integrate the user’s defined input into the
pipeline. Either generate the network with Moksiskan, basing on the
user’s defined input or get the user-defined network in GRAPHML format.
</li>
<li> <b>NETWORK CONTROLLABILITY:</b> Compute the minimal set of driven
nodes for the given target genes in the network generated at the
previous step. </li>
<li> <b>POSTPROCESSING AND OUTPUT:</b> Highlight those driven nodes
that can be targeted by FDA approved drugs. Generate the network file
(GRAPHML, Cytoscape and PDF) from the original network and by adding
additional annotations to the nodes representing selected driven
genes/proteins, drug-targetable driven genes/proteins, if any, and
target genes. Generate CSV tables with the information about the driven
genes/proteins, and the list of target genes and their control paths
from the driven nodes. </li>
</ol>
<h2> Input </h2>
<p> <b>The pipeline currently accepts the following inputs
from the user:</b> </p>
<ol>
<li> <b>List of Genes/Proteins to Generate the Network:</b> List of genes/proteins that will be used as seed
nodes by Moksiskaan to generate the network. This input can be any
gene/protein name from Homo sapiens genome.</li>
<li> <b>Custom network:</b> The user has an option to use a
custom network in the pipeline instead of the Moksiskaan network. </li>
<li> <b>Cancer Cell Lines:</b> A cancer cell line whose set of
essential proteins will be used as target nodes for the network
controllability algorithm. These nodes can act also as seed nodes if
the user decides so. </li>
<li> <b>List of Additional Target Genes:</b> A set of target nodes defined
in addition to those in the “Cancer Cell Lines". These nodes
can act also as seed nodes if the user decides so. </li>
<li> <b>Gap Between Genes:</b> The gap parameter used by Moksiskaan to generate the
network. </li>
<li> <b>Target By Drug:</b> Defines if the pipeline includes also
the drug target information for the driven nodes. If so, then the
driven nodes for which there exist FDA approved drugs will be
specifically highlighted in the output of the pipeline. </li>
<li><b>User defined drug target genes to be included in the analysis:</b> User has an option to include also set of custom drug target proteins.
If the "Target By Drug" field is chosen, the user-defined custom drug targets will be considered along with the FDA-aproved drugs targets.</li>
</ol>
<h2> Output </h2>
<ul>
<li> <i>driven.csv:</i> The drug-targetable driven
nodes and the number of cancer essential genes they control. </li>
<li> <i>extra.csv:</i> Cancer essential genes
controlled by non-drug target genes. </li>
<li> <i>details.txt:</i> Details result based on
our heuristic search algorithms, the control path for each controlled
target node is provided. </li>
<li> <i>graph.xml:</i> The generated network and
can be visualized in Cytoscape or Gephi </li>
<li> <i>visual.pdf:</i> Visualization of
controlled graph from GraphML software as a PDF. The color codes are defined as follows:
<ul>
<li><b><font color="green" style="background-color: black;">Green circle</font></b> - mark seed nodes</li>
<li><b><font color="aqua" style="background-color: black;">aqua color</font></b> - mark driven nodes that are also drug targets (either for FDA approved or custom user-defined drugs)</li>
<li><b><font color="purple" style="background-color: black;">purple color</font></b> - mark target nodes that are being controlled from the driven nodes that are drug targets</li>
<li><b><font color="red" style="background-color: black;">red color</font></b> - mark driven nodes that are not drug targets</li>
<li><b><font color="yellow" style="background-color: black;">yellow color</font></b> - mark target nodes that are being controlled from the driven nodes that are not drug targets</li>
</ul> </li>
</ul>
<p> </p>
<h2>Sample Case Studies:</h2>
<h3>Case study 1: Breast cancer</h3>
<b>INPUT:</b>
<table valign="top" border="1" cellpadding="4" cellspacing="2" width="75%">
<tbody>
<tr>
<th> List of Genes/Proteins to Generate the Network </th>
<th> List of Additional Target Genes </th>
<th> Gap Between Genes</th>
</tr>
<tr>
<td> AKT1<br> AKT3<br> NRG1</td>
<td> MTOR<br> ERBB3</td>
<td> One </td>
</tr>
</tbody>
</table>
<p> </p>
<b>OUTPUT:</b><br>
(Please note that NetControl4BioMed is a stochastic tool and for the same input it may give one of several different outputs. The following is just one of possible outputs for the input above.)
<table valign="top" border="1" cellpadding="4" cellspacing="2" width="75%">
<tbody>
<tr>
<td> <i>driven.csv </i> </td>
<td> <i>extra.csv </i> </td>
<td> <i>details.txt</i> </td>
</tr>
<tr>
<td> AKT1 </td>
<td> NRG1 </td>
<td> NRG1 <br> AKT1 <br> ERBB3 <- NRG1 <br> MTOR <- AKT1 </td>
</tr>
</tbody>
</table>
<br>
<img style="width: 760px; height: 455px;" alt="Network sample 1" src="network_sample1.png"><br>
<br>
<br>
<br>
<br>
<br>
<h3>Case study 2: Type 2 diabetic</h3>
<b>INPUT</b>
<table valign="top" border="1" cellpadding="4" cellspacing="2" width="75%">
<tbody>
<tr>
<th> List of Genes/Proteins to Generate the Network </th>
<th> List of Additional Target Genes </th>
<th> Gap Between Genes</th>
</tr>
<tr>
<td align="undefined" valign="undefined">KCNQ1 <br> NOTCH2 <br> TCF7L2 <br> HNF1A <br> HNF4A</td>
<td align="undefined" valign="undefined">CDKN2B</td>
<td align="undefined" valign="undefined">Two</td>
</tr>
</tbody>
</table>
<p> </p>
<b>OUTPUT:</b><br>
(Please note that NetControl4BioMed is a stochastic tool and for the same input it may give one of several different outputs. The following is just one of possible outputs for the input above.)
<table valign="top" border="1" cellpadding="4" cellspacing="2" width="75%">
<tbody>
<tr>
<td> <i>driven.csv </i> </td>
<td> <i>extra.csv </i> </td>
<td> <i>details.txt</i> </td>
</tr>
<tr>
<td align="undefined" valign="undefined">MYC</td>
<td align="undefined" valign="undefined"></td>
<td align="undefined" valign="undefined">CDKN2B <- MYC</td>
</tr>
</tbody>
</table>
<br>
<img style="width: 752px; height: 275px;" alt="Network sample 2" src="network_cs2.png"><br>
<br>
<br>
<br>
<br>
<br>
<h3>Case study 3: Alzheimer's disease</h3>
<b>INPUT</b>
<table valign="top" border="1" cellpadding="4" cellspacing="2" width="75%">
<tbody>
<tr>
<th> List of Genes/Proteins to Generate the Network </th>
<th> List of Additional Target Genes </th>
<th> Gap Between Genes</th>
</tr>
<tr>
</tr>
<tr>
<td align="undefined" valign="undefined">BDNF <br> CHRNA6 <br> CHRNA7 <br> CHRNB4 <br> CR1 <br> EFNA5 <br> EGFR <br>
EPHA1 <br> EPHA4 <br> GAB2 <br> IRS1 <br> NOS3 <br> NTRK2 <br> PIK3R1 <br> PPP1R3A <br> PPP3CB <br> PTGS2 <br> SOS2 </td>
<td align="undefined" valign="undefined">NOS3</td>
<td align="undefined" valign="undefined">Two</td>
</tr>
</tbody>
</table>
<p> </p>
<b>OUTPUT:</b><br>
(Please note that NetControl4BioMed is a stochastic tool and for the same input it may give one of several different outputs. The following is just one of possible outputs for the input above.)
<table valign="top" border="1" cellpadding="4" cellspacing="2" width="75%">
<tbody>
<tr>
<td> <i>driven.csv </i> </td>
<td> <i>extra.csv </i> </td>
<td> <i>details.txt</i> </td>
</tr>
<tr>
<td align="undefined" valign="undefined">MTOR</td>
<td align="undefined" valign="undefined">CR1</td>
<td align="undefined" valign="undefined">NOS3
<- AKT1 <- MTOR</td>
</tr>
</tbody>
</table>
<img style="width: 1590px; height: 425px;" alt="Network sample 3" src="network_sample3.png"><br>
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