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TMB Tool Bug Fix #68

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TMB Tool Bug Fix #68

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d476e08
TMB tool bug fix
Rima-Waleed Oct 8, 2025
c1efedd
fix
Rima-Waleed Oct 8, 2025
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63 changes: 49 additions & 14 deletions tmb/calculate_tmb/calc_nonsyn_tmb.py
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Original file line number Diff line number Diff line change
Expand Up @@ -43,7 +43,7 @@
# WGS/WES CDS
WES_WGS_CDS = 30

# egilible variants (for counting mutations)
# eligible variants (for counting mutations)
VC_NONSYNONYMOUS_LIST = [
"Frame_Shift_Del",
"Frame_Shift_Ins",
Expand Down Expand Up @@ -93,7 +93,7 @@
######
# extract coding sequence length from gene panels and map to each sample
######
def extractCDS(_inputStudyFolder, _panelFolderPath, _sampleMap):
def extractCDS(_inputStudyFolder, _panelFolderPath, _sampleMap, _seqSampleIds):

_cdsMap = {}

Expand Down Expand Up @@ -127,7 +127,16 @@ def extractCDS(_inputStudyFolder, _panelFolderPath, _sampleMap):
_items = _line.rstrip("\n").rstrip('\r').split('\t')
_sampleID = _items[_posSampleId]
_panelID = _items[_posMutPanel]

# assign CDS value, use 'NA' if panel ID is missing or invalid
if _panelID in ["NA", "", "None"] or _panelID not in _cdsMap:
_cds = "NA"
else:
_cds = _cdsMap[_panelID]
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@rmadupuri rmadupuri Oct 15, 2025

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IndentationError: expected an indented block after 'else' statement


# If sample is sequenced but CDS is NA, assign default WES/WGS CDS
if _cds == "NA" and _sampleID in _seqSampleIds:
_cds = WES_WGS_CDS
Comment on lines +131 to +139
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@rmadupuri rmadupuri Oct 15, 2025

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Getting a TabError: inconsistent use of tabs and spaces in indentation


if _sampleMap.has_key(_sampleID):
_sampleMap[_sampleID]["cds"] = _cds
Expand Down Expand Up @@ -187,13 +196,24 @@ def calcTMB(_sampleMap):

_tmbs = []

for _sampleID in _sampleMap:
_tmb = _sampleMap[_sampleID]["vc_count"] / _sampleMap[_sampleID]["cds"]
if _sampleMap[_sampleID]["cds"] < PANEL_THRESHOLD:
_sampleMap[_sampleID]["tmb"] = PANEL_THRESHOLD_MSG
else:
_sampleMap[_sampleID]["tmb"] = _sampleMap[_sampleID]["vc_count"] / _sampleMap[_sampleID]["cds"]
_tmbs.append(_tmb)
for _sampleID in _sampleMap:
cds = _sampleMap[_sampleID]["cds"]
vc_count = _sampleMap[_sampleID]["vc_count"]

# correctly compute TMB
if cds == "NA":
_tmb = "NA"
else:
_tmb = vc_count / cds

# apply panel threshold
if cds != "NA" and cds < PANEL_THRESHOLD:
_sampleMap[_sampleID]["tmb"] = PANEL_THRESHOLD_MSG
else:
_sampleMap[_sampleID]["tmb"] = _tmb
if _tmb != "NA":
_tmbs.append(_tmb)

if len(_tmbs) != 0:
sys.stdout.write(str(max(_tmbs)) + "\t" + str(min(_tmbs)) + "\t" + str(numpy.median(_tmbs)) + "\n")
else:
Expand All @@ -204,7 +224,7 @@ def calcTMB(_sampleMap):
######
# add TMB column to clinical file
######
def addTMB(_inputStudyFolder, _sampleTmbMap):
def addTMB(_inputStudyFolder, _sampleTmbMap, _seqSampleIds):

# extract list of sequenced sample IDs
_seqSampleIds = []
Expand All @@ -218,7 +238,6 @@ def addTMB(_inputStudyFolder, _sampleTmbMap):
print("Can't find sequenced case list file!")
sys.exit(2)


# header for the new column in clinical sample file
_headerItems = [
CLIN_TMB_COL_ID,
Expand Down Expand Up @@ -254,7 +273,11 @@ def addTMB(_inputStudyFolder, _sampleTmbMap):
else:
_sampleID = _line.split("\t")[_posSampleID]
if _sampleID in _sampleTmbMap:
_newline = _line.rstrip("\n") + "\t" + str(_sampleTmbMap[_sampleID]["tmb"])
# skip numeric TMB for unsequenced samples
if _sampleID not in _seqSampleIds:
_newline = _line.rstrip("\n") + "\tNA"
else:
_newline = _line.rstrip("\n") + "\t" + str(_sampleTmbMap[_sampleID]["tmb"])
else:
if _sampleID in _seqSampleIds:
_newline = _line.rstrip("\n") + "\t" + "0"
Expand All @@ -276,12 +299,24 @@ def main():
_sampleTmbMap = {}

sys.stdout.write(os.path.basename(_inputStudyFolder) + "\t")

# extract list of sequenced sample IDs
_seqSampleIds = []
if os.path.isfile(_inputStudyFolder + "/case_lists/" + SEQ_CASE_LIST_FILE_NAME):
_caseListPath = _inputStudyFolder + "/case_lists/" + SEQ_CASE_LIST_FILE_NAME
with open(_caseListPath,'r') as _caseList:
for _line in _caseList:
if _line.startswith(SEQ_CASE_LIST_FIELD_NAME):
_seqSampleIds = _line.split(':')[1].strip().split("\t")
else:
print("Can't find sequenced case list file!")
sys.exit(2)

if os.path.isdir(_inputStudyFolder) and os.path.isdir(_genePanelFolder):
# Find matrix file -> identify CDS for targeted panels
if os.path.isfile(_inputStudyFolder + "/" + MATRIX_FILE_NAME):
sys.stdout.write("Targeted\t")
_sampleTmbMap = calcTMB(extractCDS(_inputStudyFolder, _genePanelFolder, cntVariants(_inputStudyFolder)))
_sampleTmbMap = calcTMB(extractCDS(_inputStudyFolder, _genePanelFolder, cntVariants(_inputStudyFolder),_seqSampleIds))
else: # No matrix file -> WGS/WES studies
sys.stdout.write("WGS/WES\t")
_sampleTmbMap = calcTMB(cntVariants(_inputStudyFolder))
Expand All @@ -292,7 +327,7 @@ def main():
if _sampleTmbInst["tmb"] != PANEL_THRESHOLD_MSG:
_update_flag = "true"
if _update_flag == "true":
addTMB(_inputStudyFolder, _sampleTmbMap)
addTMB(_inputStudyFolder, _sampleTmbMap, _seqSampleIds)

else:
print("Error input folder path(s)!")
Expand Down