def datasets(projects_set):
log = task.logger
conf = task.conf
classifier, projects = projects_set
classifier_id = classifier["id"]
group_values = classifier["group_values"]
short_values = classifier["group_short_values"]
long_values = classifier["group_long_values"]
group_name = classifier["group_name"]
group_short_name = classifier["group_short_name"]
group_long_name = classifier["group_long_name"]
group_file_prefix = normalize_id(classifier_id)
log.info("--- [{0} ({1}) ({2}) ({3})] {4}".format(classifier["name"], group_long_name, group_short_name, group_name, "-" * 30))
log.info("Reading number of samples per project ...")
project_ids = []
total_samples = 0
for project in projects:
project_id = project["id"]
project_ids += [project_id]
log.info(" Project {0}".format(project["id"]))
projdb = ProjectDb(project["db"])
num_samples = projdb.get_total_affected_samples()
total_samples += num_samples
log.debug(" {0} samples".format(num_samples))
projdb.close()
log.debug(" {0} samples in total".format(total_samples))
log.info("Updating ...")
combination_path = get_combination_path(conf)
path = os.path.join(combination_path, "{0}.tsv".format(group_file_prefix))
if not os.path.exists(path):
with open(path, "w") as f:
tsv.write_line(f, "NAME", "SHORT_NAME", "LONG_NAME", "SAMPLES_TOTAL", "PROJECT_IDS")
with open(path, "a") as f:
tsv.write_line(f, group_name, group_short_name, group_long_name, total_samples, ",".join(project_ids))
def combination_recurrences(projects_set):
log = task.logger
conf = task.conf
classifier, projects = projects_set
classifier_id = classifier["id"]
group_values = classifier["group_values"]
short_values = classifier["group_short_values"]
long_values = classifier["group_long_values"]
group_name = classifier["group_name"]
group_short_name = classifier["group_short_name"]
group_long_name = classifier["group_long_name"]
if len(group_values) == 0:
group_file_prefix = classifier_id
else:
group_file_prefix = "{0}-{1}".format(classifier_id, group_short_name)
group_file_prefix = normalize_id(group_file_prefix)
log.info("--- [{0} ({1}) ({2}) ({3})] {4}".format(classifier["name"], group_long_name, group_short_name, group_name, "-" * 30))
log.info("Creating database ...")
db_path = make_temp_file(task, suffix="-{0}.db".format(group_file_prefix))
log.debug(" > {0}".format(db_path))
conn = sqlite3.connect(db_path)
conn.row_factory = sqlite3.Row
create_db(conn)
log.info("Combining recurrences ...")
c = conn.cursor()
sample_total = 0
project_ids = []
for project in projects:
project_ids += [project["id"]]
log.info(" Project {0}:".format(project["id"]))
projdb = ProjectDb(project["db"])
project_sample_total = projdb.get_total_affected_samples()
sample_total += project_sample_total
log.info(" Total samples = {0}".format(project_sample_total))
log.info(" Variant genes ...")
count = 0
for afg in projdb.affected_genes(join_variant=True, join_xrefs=True, join_rec=True):
var = afg.var
rec = afg.rec
if rec.sample_freq is None:
log.warn("Discarding variant gene without sample frequency: {0}".format(repr(afg)))
continue
start, end, ref, alt = var_to_tab(var)
try:
c.execute("INSERT INTO variants (chr, strand, start, ref, alt, xrefs) VALUES (?,?,?,?,?,?)",
(var.chr, var.strand, start, ref, alt, ",".join(var.xrefs)))
var_id = c.lastrowid
except sqlite3.IntegrityError:
c.execute("SELECT var_id FROM variants WHERE chr=? AND strand=? AND start=? AND ref=? AND alt=?",
(var.chr, var.strand, start, ref, alt))
r = c.fetchone()
var_id = r[0]
try:
c.execute("INSERT INTO variant_genes (var_id, gene_id, impact, coding_region, prot_changes, sample_freq) VALUES (?,?,?,?,?,?)",
(var_id, afg.gene_id, afg.impact, afg.coding_region, afg.prot_changes, rec.sample_freq))
except sqlite3.IntegrityError:
c.execute("""
UPDATE variant_genes
SET sample_freq=sample_freq + ?
WHERE var_id=? AND gene_id=?""",
(rec.sample_freq, var_id, afg.gene_id))
count += 1
log.info(" {0} variant genes".format(count))
log.info(" Genes ...")
count = 0
for gene in projdb.genes(join_xrefs=True, join_rec=True):
rec = gene.rec
if rec.sample_freq is None:
continue
c.execute("SELECT COUNT(*) FROM genes WHERE gene_id=?", (gene.id,))
r = c.fetchone()
if r[0] == 0:
c.execute("INSERT INTO genes (gene_id, sample_freq) VALUES (?,?)",
(gene.id, rec.sample_freq))
else:
c.execute("UPDATE genes SET sample_freq=sample_freq + ? WHERE gene_id=?",
(rec.sample_freq, gene.id))
count += 1
log.info(" {0} genes".format(count))
log.info(" Pathways ...")
count = 0
for pathway in projdb.pathways(join_rec=True):
rec = pathway.rec
if rec.sample_freq is None:
continue
c.execute("SELECT COUNT(*) FROM pathways WHERE pathway_id=?", (pathway.id,))
r = c.fetchone()
if r[0] == 0:
c.execute("INSERT INTO pathways (pathway_id, sample_freq) VALUES (?,?)",
(pathway.id, rec.sample_freq))
else:
c.execute("UPDATE pathways SET sample_freq=sample_freq + ? WHERE pathway_id=?",
(rec.sample_freq, pathway.id))
count += 1
log.info(" {0} pathways".format(count))
projdb.close()
log.info("Calculating proportions with {0} samples in total among projects ...".format(sample_total))
if sample_total > 0:
c.execute("UPDATE variant_genes SET sample_prop=CAST(sample_freq AS REAL)/{0}.0".format(sample_total))
c.execute("UPDATE genes SET sample_prop=CAST(sample_freq AS REAL)/{0}.0".format(sample_total))
c.execute("UPDATE pathways SET sample_prop=CAST(sample_freq AS REAL)/{0}.0".format(sample_total))
c.close()
conn.commit()
log.info("Saving results ...")
c = conn.cursor()
base_path = get_combination_path(conf, "recurrences")
log.info(" Variant genes ...")
with tsv.open(os.path.join(base_path, "variant_gene-{0}.tsv.gz".format(group_file_prefix)), "w") as f:
tsv.write_param(f, "classifier", classifier["id"])
tsv.write_param(f, "group_id", group_name)
tsv.write_param(f, "group_short_name", group_short_name)
tsv.write_param(f, "group_long_name", group_long_name)
tsv.write_param(f, "projects", ",".join(project_ids))
tsv.write_param(f, "SAMPLE_TOTAL", sample_total)
tsv.write_line(f, "CHR", "STRAND", "START", "ALLELE", "GENE_ID", "IMPACT", "IMPACT_CLASS", "SAMPLE_FREQ", "SAMPLE_PROP", "PROT_CHANGES", "XREFS")
for r in c.execute("SELECT * FROM variant_genes JOIN variants USING (var_id) ORDER BY chr*1, chr, strand, start, gene_id"):
strand, ref, alt = r["strand"], r["ref"], r["alt"]
allele = "{0}/{1}".format(ref, alt)
tsv.write_line(f, r["chr"], strand, r["start"], allele,
r["gene_id"], r["impact"], TransFIC.class_name(r["impact"]),
r["sample_freq"], r["sample_prop"], r["prot_changes"], r["xrefs"], null_value="-")
log.info(" Genes ...")
with tsv.open(os.path.join(base_path, "gene-{0}.tsv.gz".format(group_file_prefix)), "w") as f:
tsv.write_param(f, "classifier", classifier["id"])
tsv.write_param(f, "group_id", group_name)
tsv.write_param(f, "group_short_name", group_short_name)
tsv.write_param(f, "group_long_name", group_long_name)
tsv.write_param(f, "projects", ",".join(project_ids))
tsv.write_param(f, "SAMPLE_TOTAL", sample_total)
tsv.write_line(f, "GENE_ID", "SAMPLE_FREQ", "SAMPLE_PROP")
for r in c.execute("SELECT * FROM genes ORDER BY gene_id"):
tsv.write_line(f, r["gene_id"], r["sample_freq"], r["sample_prop"], null_value="-")
log.info(" Pathways ...")
with tsv.open(os.path.join(base_path, "pathway-{0}.tsv.gz".format(group_file_prefix)), "w") as f:
tsv.write_param(f, "classifier", classifier["id"])
tsv.write_param(f, "group_id", group_name)
tsv.write_param(f, "group_short_name", group_short_name)
tsv.write_param(f, "group_long_name", group_long_name)
tsv.write_param(f, "projects", ",".join(project_ids))
tsv.write_param(f, "SAMPLE_TOTAL", sample_total)
tsv.write_line(f, "PATHWAY_ID", "SAMPLE_FREQ", "SAMPLE_PROP")
for r in c.execute("SELECT * FROM pathways ORDER BY pathway_id"):
tsv.write_line(f, r["pathway_id"], r["sample_freq"], r["sample_prop"], null_value="-")
conn.close()
remove_temp(task, db_path)
def combination_oncodrivefm(projects_set):
log = task.logger
conf = task.conf
classifier, projects = projects_set
classifier_id = classifier["id"]
group_values = classifier["group_values"]
short_values = classifier["group_short_values"]
long_values = classifier["group_long_values"]
group_name = classifier["group_name"]
group_short_name = classifier["group_short_name"]
group_long_name = classifier["group_long_name"]
if len(group_values) == 0:
group_file_prefix = classifier_id
else:
group_file_prefix = "{0}-{1}".format(classifier_id, group_short_name)
group_file_prefix = normalize_id(group_file_prefix)
log.info("--- [{0} ({1}) ({2}) ({3})] {4}".format(classifier["name"], group_long_name, group_short_name, group_name, "-" * 30))
log.info("Exporting project data ...")
base_path = make_temp_dir(task, suffix=".{0}".format(group_file_prefix))
log.debug("> {0}".format(base_path))
project_ids = []
gene_files = []
pathway_files = []
for project in projects:
project_id = project["id"]
project_ids += [project_id]
log.info(" Project {0}:".format(project["id"]))
projdb = ProjectDb(project["db"])
log.info(" Genes ...")
count = 0
file_path = os.path.join(base_path, "{0}-genes.tsv".format(project_id))
gene_files += [file_path]
with open(file_path, "w") as f:
tsv.write_param(f, "classifier", classifier_id)
tsv.write_param(f, "group_id", group_name)
tsv.write_param(f, "slice", project_id)
tsv.write_line(f, "GENE_ID", "PVALUE")
for gene in projdb.genes():
if gene.fm_pvalue is not None:
tsv.write_line(f, gene.id, gene.fm_pvalue, null_value="-")
count += 1
log.info(" {0} genes".format(count))
log.info(" Pathways ...")
count = 0
file_path = os.path.join(base_path, "{0}-pathways.tsv".format(project_id))
pathway_files += [file_path]
with open(file_path, "w") as f:
tsv.write_param(f, "classifier", classifier_id)
tsv.write_param(f, "group_id", group_name)
tsv.write_param(f, "slice", project_id)
tsv.write_line(f, "PATHWAY_ID", "ZSCORE")
for pathway in projdb.pathways():
if pathway.fm_zscore is not None:
tsv.write_line(f, pathway.id, pathway.fm_zscore, null_value="-")
count += 1
log.info(" {0} pathways".format(count))
projdb.close()
log.info("Combining ...")
combination_path = get_combination_path(conf, "oncodrivefm")
log.info(" Genes ...")
cmd = " ".join([
"oncodrivefm-combine",
"-m median-empirical",
"-o '{0}'".format(combination_path),
"-n 'gene-{0}'".format(group_file_prefix),
"-D 'classifier={0}'".format(classifier_id),
"-D 'group_id={0}'".format(group_name),
"-D 'group_short_name={0}'".format(group_short_name),
"-D 'group_long_name={0}'".format(group_long_name),
"--output-format tsv.gz"
] + ["'{0}'".format(name) for name in gene_files])
log.debug(cmd)
ret_code = subprocess.call(cmd, shell=True)
if ret_code != 0:
#log.error("OncodriveFM error while combining gene pvalues:\n{0}".format(cmd))
#return -1
raise Exception("OncodriveFM error while combining gene pvalues:\n{0}".format(cmd))
log.info(" Pathways ...")
cmd = " ".join([
"oncodrivefm-combine",
"-m median-zscore",
"-o '{0}'".format(combination_path),
"-n 'pathway-{0}'".format(group_file_prefix),
"-D 'classifier={0}'".format(classifier_id),
"-D 'group_id={0}'".format(group_name),
"-D 'group_short_name={0}'".format(group_short_name),
"-D 'group_long_name={0}'".format(group_long_name),
"--output-format tsv.gz"
] + ["'{0}'".format(name) for name in pathway_files])
log.debug(cmd)
ret_code = subprocess.call(cmd, shell=True)
if ret_code != 0:
#log.error("OncodriveFM error while combining pathway zscores:\n{0}".format(cmd))
#return -1
raise Exception("OncodriveFM error while combining pathway zscores:\n{0}".format(cmd))
remove_temp(task, base_path)
def drivers():
log = task.logger
conf = task.conf
db_path = get_results_path(conf, "drivers.db")
db = SigDb(db_path)
db.open()
log.info("Variants ...")
path = get_combination_path(conf, "recurrences", "variant_gene-global-all.tsv.gz")
with tsv.open(path, "r") as f:
types = (str, str, int, str)
for fields in tsv.lines(f, types, columns=("CHR", "STRAND", "START", "ALLELE"), header=True):
chr, strand, start, allele = fields[:4]
db.add_variant(chr, start)
log.info("Genes ...")
gene_sites = {}
gene_fm = set()
gene_clust = set()
#SPECIAL_THRESHOLD = ["C18", "C34"]
SPECIAL_THRESHOLD = []
log.info(" OncodriveFM ...")
filename_re = re.compile(r"gene-cancer_site-(.+)\.tsv.gz")
base_path = get_combination_path(conf, "oncodrivefm")
for path in os.listdir(base_path):
m = filename_re.match(path)
if not m:
continue
cancer_site_code = m.group(1)
if cancer_site_code in SPECIAL_THRESHOLD:
threshold = 1e-6
else:
threshold = 0.01
with tsv.open(os.path.join(base_path, path), "r") as f:
params = tsv.params(f)
cancer_site_name = params["group_long_name"]
for fields in tsv.lines(f, (str, float), columns=("ID", "QVALUE"), header=True):
gene, qvalue = fields
if qvalue < threshold:
add_cancer_site(gene_sites, gene, cancer_site_code, cancer_site_name)
gene_fm.add(gene)
log.info(" OncodriveCLUST ...")
filename_re = re.compile(r"cancer_site-(.+)\.tsv.gz")
base_path = get_combination_path(conf, "oncodriveclust")
for path in os.listdir(base_path):
m = filename_re.match(path)
if not m:
continue
cancer_site_code = m.group(1)
with tsv.open(os.path.join(base_path, path), "r") as f:
params = tsv.params(f)
cancer_site_name = params["group_long_name"]
for fields in tsv.lines(f, (str, float), columns=("ID", "QVALUE"), header=True):
gene, qvalue = fields
if qvalue < 0.05:
add_cancer_site(gene_sites, gene, cancer_site_code, cancer_site_name)
gene_clust.add(gene)
log.info(" Updating db ...")
sig_genes = gene_fm | gene_clust
for gene in sig_genes:
db.add_gene(gene, gene in gene_fm, gene in gene_clust)
log.info("Saving driver genes cancer sites dataset ...")
path = get_results_path(conf, "gene-driver_cancer_sites.tsv")
log.debug("> {}".format(path))
with open(path, "w") as f:
tsv.write_param(f, "date", datetime.now())
tsv.write_line(f, "GENE_ID", "FM", "CLUST", "CANCER_SITES_COUNT", "CANCER_SITE_CODES", "CANCER_SITE_NAMES")
for gene, sites in gene_sites.items():
tsv.write_line(f, gene,
1 if gene in gene_fm else 0,
1 if gene in gene_clust else 0,
len(sites),
", ".join(sorted([code for code, name in sites])),
", ".join(sorted([name for code, name in sites])))
db.commit()
db.close()