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Dev/upload omim inheritance #5

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Dev/upload omim inheritance #5

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a9b48cc
- Load diseases data from OMIM source that has inheritance model.
Jan 23, 2017
c926a43
Remove the step that remove the (number) from disease name as this wi…
Jan 24, 2017
614b90e
Store OMIM inheritance models in the database in abbreviated forms.
Feb 6, 2017
fd3189e
Revert back user configuration to default settings and only change th…
Feb 6, 2017
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191 changes: 124 additions & 67 deletions geneloader.php
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Original file line number Diff line number Diff line change
Expand Up @@ -100,7 +100,7 @@
'gene_list' => 'all',
'transcript_list' => 'best',
'genes_to_ignore' => 'genes_to_ignore.txt',
'omim_data' => 'morbidmap.txt',
'omim_data' => 'genemap2.txt',
),
'hgnc_columns' => array(
'gd_hgnc_id' => 'HGNC ID',
Expand Down Expand Up @@ -143,9 +143,9 @@
),
// Column headers for the OMIM disease file morbidmap.txt.
'omim_columns' => array(
'disease' => 'Phenotype',
'disease' => 'Phenotypes',
'genes' => 'Gene Symbols',
'mim' => 'MIM Number',
'mim' => 'Mim Number',
'cyto_location' => 'Cyto Location',
),
);
Expand Down Expand Up @@ -937,6 +937,23 @@ function lovd_verifySettings ($sKeyName, $sMessage, $sVerifyType, $options)
$aOMIMIDsInDB = $_DB->query('SELECT id_omim, id, chromosome FROM ' . TABLE_GENES . ' WHERE id_omim IS NOT NULL')->fetchAllGroupAssoc();
$aInsertData = array();

$aInheritanceMap = array(
'autosomal dominant' => 'AD',
'isolated cases' => 'IC',
'multifactorial' => 'Mu',
'autosomal recessive' => 'AR',
'digenic recessive' => 'DR',
'digenic dominant' => 'DD',
'somatic mutation' => 'SMu',
'x-linked dominant' => 'XLD',
'mitochondrial' => 'Mi',
'somatic mosaicism' => 'SMo',
'x-linked recessive' => 'XLR',
'inherited chromosomal imbalance' => 'ICB',
'x-linked' => 'XL',
'y-linked' => 'YL'
);

foreach ($aOMIMFile as $sLine) {
$aData = array();

Expand All @@ -950,83 +967,122 @@ function lovd_verifySettings ($sKeyName, $sMessage, $sVerifyType, $options)
$aLineExplode = explode("\t", $sLine);
$aLine = array();
foreach ($aOMIMColumns as $nKey => $sName) {
$aLine[$sName] = $aLineExplode[$nKey];
}

if (!isset($aLineExplode[$nKey])) {
$aLine[$sName] = '';
} else {
$aLine[$sName] = $aLineExplode[$nKey];
}

}

// Process the disease text and remove unwanted characters.
$aData['disease'] = $aLine['disease'];
// Take phenotype mapping number off.
$aData['disease'] = preg_replace('/\s*\(\d\)$/', '', $aData['disease']);
// Isolate OMIM ID.
$aData['disease_id_omim'] = null;
if (preg_match('/,? (\d{6})$/', $aData['disease'], $aRegs)) {
$aData['disease_id_omim'] = $aRegs[1];
// Now trim off the OMIM ID, the space and the optional comma.
$aData['disease'] = substr($aData['disease'], 0, -strlen($aRegs[0]));
} else {
// Entry doesn't have disease OMIM ID.
// These entries are problematic with other things as well (such as chromosome). Drop them.
continue;
}
// Some entries start with a questionmark, or are surrounded by brackets.
// Entries seem to be alright otherwise.
$aData['disease'] = trim($aData['disease'], '?[]{}');
// Multiple phenotypes in one column separated by semicolon, we want to import all of them if the OMIM ID does not already exist
$aDiseaseNames = explode('; ', $aLine['disease']);
foreach ($aDiseaseNames as $sDiseaseName) {
$aData['inheritance'] = array();
$aData['disease'] = $sDiseaseName;

// Isolate OMIM ID.
$aData['disease_id_omim'] = null;

// Phenotypes column contains disease name, OMIM ID, and inheritance model
$aDiseaseParts = explode(', ', $aData['disease']);
$nIndexOmimId = false;
$aNameParts = array();
foreach ($aDiseaseParts as $nIndex => $sPart) {
if (preg_match('/(\d{6}) (\(\d+\))/', $sPart, $aRegs)) {
// OMIM ID found in the phenotypes column
$nIndexOmimId = $nIndex;
$aData['disease_id_omim'] = $aRegs[1];
} else {
// Some entries start with a questionmark, or are surrounded by brackets.
// Entries seem to be alright otherwise.
$aNameParts[] = trim($sPart, '?[]{}');
}
}

if ($nIndexOmimId !== false) {
// Parts before the OMIM ID is disease name.
$aData['disease'] = implode(', ', array_slice($aNameParts, 0, $nIndexOmimId));

// Parts after the OMIM ID is inheritance.
$aInheritances = array_slice($aNameParts, $nIndexOmimId);
foreach ($aInheritances as $sInheritance) {
$sInheritance = strtolower($sInheritance);
if (!empty($aInheritanceMap[$sInheritance])) {
$aData['inheritance'][] = $aInheritanceMap[$sInheritance];
} else {
$aData['inheritance'][] = $sInheritance;
}
}
} else {
// Entry doesn't have disease OMIM ID.
// These entries are problematic with other things as well (such as chromosome). Drop them.
continue;
}


// The MIM column is not always the gene's OMIM ID!
// Sometimes it's the disease's OMIM ID, and the disease name doesn't contain any.
// But we'll get rid of those cases, because they're not associated with a gene we can work with.
$aData['gene_id_omim'] = $aLine['mim'];
$aData['genes'] = preg_split('/, ?/', $aLine['genes']);
// The MIM column is not always the gene's OMIM ID!
// Sometimes it's the disease's OMIM ID, and the disease name doesn't contain any.
// But we'll get rid of those cases, because they're not associated with a gene we can work with.
$aData['gene_id_omim'] = $aLine['mim'];
$aData['genes'] = preg_split('/, ?/', $aLine['genes']);



// Parse chromosome out of the 11q13.32 format.
if (preg_match('/^(\d+|X|Y)\w/', $aLine['cyto_location'], $aRegs)) {
$aData['chr'] = $aRegs[1];
} else {
// This actually never happened, but just in case.
continue;
}
// Parse chromosome out of the 11q13.32 format.
if (preg_match('/^(\d+|X|Y)\w/', $aLine['cyto_location'], $aRegs)) {
$aData['chr'] = $aRegs[1];
} else {
// This actually never happened, but just in case.
continue;
}

// First try to see if there is an exact match with the OMIM ID, chromosome and gene symbol.
if (!empty($aOMIMIDsInDB[$aData['gene_id_omim']]) &&
in_array($aOMIMIDsInDB[$aData['gene_id_omim']]['id'], $aData['genes']) &&
$aOMIMIDsInDB[$aData['gene_id_omim']]['chromosome'] == $aData['chr']) {
$aData['db_gene'] = $aOMIMIDsInDB[$aData['gene_id_omim']]['id'];
} else {
// Otherwise, loop through the gene symbols to see if we find a match in the database
// just on symbol instead of the OMIM ID.
foreach ($aData['genes'] as $sGene) {
if (!empty($aGenesInDBWithoutOMIM[$sGene]) && $aGenesInDBWithoutOMIM[$sGene] == $aData['chr']) {
$aData['db_gene'] = $sGene;
// First try to see if there is an exact match with the OMIM ID, chromosome and gene symbol.
if (!empty($aOMIMIDsInDB[$aData['gene_id_omim']]) &&
in_array($aOMIMIDsInDB[$aData['gene_id_omim']]['id'], $aData['genes']) &&
$aOMIMIDsInDB[$aData['gene_id_omim']]['chromosome'] == $aData['chr']) {
$aData['db_gene'] = $aOMIMIDsInDB[$aData['gene_id_omim']]['id'];
} else {
// Otherwise, loop through the gene symbols to see if we find a match in the database
// just on symbol instead of the OMIM ID.
foreach ($aData['genes'] as $sGene) {
// "Gene symbols" column has multiple symbols. But, we only need one that is found in our database.
// "Approved Symbol" column has only 1 symbol, but it is not necessarily the one in our database.
if (!empty($aGenesInDBWithoutOMIM[$sGene]) && $aGenesInDBWithoutOMIM[$sGene] == $aData['chr']) {
$aData['db_gene'] = $sGene;
}
}
}
}

if (!isset($aData['db_gene'])) {
// We can not find a gene in the DB for this disease, so we ignore it.
continue;
}

// If we're still here, then add this disease to the data to be inserted.
if (!isset($aInsertData[$aData['disease_id_omim']])) {
// This is the first time we have seen this disease so create a new entry for it and assign the gene.
$aInsertData[$aData['disease_id_omim']] = array('disease' => $aData['disease'], 'genes' => array($aData['db_gene']));
} else {
// We have seen this disease previously.
// Check if the name of the disease is shorter than the existing name, and if so, then use this one.
if (strlen($aData['disease']) < strlen($aInsertData[$aData['disease_id_omim']]['disease'])) {
$aInsertData[$aData['disease_id_omim']]['disease'] = $aData['disease'];
if (!isset($aData['db_gene'])) {
// We can not find a gene in the DB for this disease, so we ignore it.
continue;
}
// Check if this gene has already been added and if not then add it
if (!in_array($aData['db_gene'], $aInsertData[$aData['disease_id_omim']]['genes'])) {
$aInsertData[$aData['disease_id_omim']]['genes'][] = $aData['db_gene'];

// If we're still here, then add this disease to the data to be inserted.
if (!isset($aInsertData[$aData['disease_id_omim']])) {
// This is the first time we have seen this disease so create a new entry for it and assign the gene.
$aInsertData[$aData['disease_id_omim']] = array('disease' => $aData['disease'], 'genes' => array($aData['db_gene']), 'inheritance' => $aData['inheritance']);
} else {
// We have seen this disease previously.
// Check if the name of the disease is shorter than the existing name, and if so, then use this one.
if (strlen($aData['disease']) < strlen($aInsertData[$aData['disease_id_omim']]['disease'])) {
$aInsertData[$aData['disease_id_omim']]['disease'] = $aData['disease'];
}
// Check if this gene has already been added and if not then add it
// Here, we are appending gene symbols from the same OMIM ID, but different row of the OMIM file.
if (!in_array($aData['db_gene'], $aInsertData[$aData['disease_id_omim']]['genes'])) {
$aInsertData[$aData['disease_id_omim']]['genes'][] = $aData['db_gene'];
}

if (!empty($aInsertData[$aData['disease_id_omim']]['inheritance'])) {
$aInsertData[$aData['disease_id_omim']]['inheritance'] = array_unique(array_merge($aInsertData[$aData['disease_id_omim']]['inheritance'], $aData['inheritance']));
}
}
}
} // end of disease name foreach


}

// $aInsertData should now contain unique diseases with their own OMIM IDs and unique genes associated with them.
Expand All @@ -1035,15 +1091,14 @@ function lovd_verifySettings ($sKeyName, $sMessage, $sVerifyType, $options)
$aGen2DisInLOVD = $_DB->query('SELECT CONCAT(geneid, diseaseid), 1 FROM ' . TABLE_GEN2DIS)->fetchAllCombine();

// Prepare the insert statements.
$qDiseases = $_DB->prepare('INSERT INTO ' . TABLE_DISEASES . ' (name, id_omim, created_by, created_date) VALUES (?, ?, ?, ?)');
$qDiseases = $_DB->prepare('INSERT INTO ' . TABLE_DISEASES . ' (name, inheritance, id_omim, created_by, created_date) VALUES (?, ?, ?, ?, ?)');
$qGen2Dis = $_DB->prepare('INSERT INTO ' . TABLE_GEN2DIS . ' (geneid, diseaseid) VALUES (?, ?)');
// The diseases will be done so quickly, let's not re-run this all the time.
$sCreatedDate = date('Y-m-d H:i:s');

$nDiseasesCreated = 0;
$nGen2DisCreated = 0;
$nLoopCount = 0;

print(' OK!
Importing OMIM data');

Expand All @@ -1065,11 +1120,13 @@ function lovd_verifySettings ($sKeyName, $sMessage, $sVerifyType, $options)
// Setup the disease data to insert.
$aSQL = array(
'name' => $OMIMEntry['disease'],
'inheritance' => implode(';', $OMIMEntry['inheritance']),
'id_omim' => $nOMIMID,
'created_by' => 0,
'created_date' => $sCreatedDate,
);
// Insert the new disease and return the new disease ID.

$qDiseases->execute(array_values($aSQL));
$nID = $_DB->lastInsertId();
$nDiseasesCreated ++;
Expand Down