Correct fusion reported but false positions for MYC gene and IGH@ locus

[pkerbs]

Hi Daniel, i have noticed the same issue in version 1.33 for IGH@ locus and MYC. Could you please have a look at it? Thank you.

IGH@

chr14:105,556,000-106,883,700 (hg38 location) FusionCatcher reports -> chr14:63187193

BCL2	IGH@	known,oncogene,chimer2,cancer,tumor,oncokb,mitelman,ccle	0	34	19	104	BOWTIE+SPOTLIGHT	18:63126237:-	14:63187193:-	ENSG00000171791	ENSG09000001014			TCAAATCTATGGTGGTTTGACCTTTAGAGAGTTGCTTTACGTGGCCTGTTTCAACACAGACCCACCCAGAGCCCTCCTGCCCTCCTTCCGCGGGGGCTTTCTCATGGCTGTCCTTCAGGGTCTTCCTGAAATGCAGTGGTGCTTACGCTCCACCAAGAAAGCAGGAAACCT*CATAACGACTTTACTACTACTACTACATGGACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCAGCC	UTR/---

MYC

chr8:127735434-127742951 (hg38 location) FusionCatcher reports -> chr8:105556959

IGH@	MYC	known,oncogene,chimer2,cancer,tumor,m342,oncokb,mitelman,ccle,t23	0	430	191	133	BOWTIE+SPOTLIGHT	14:105647945:+	8:105556959:+	ENSG09000000013	ENSG00000136997			TGCTGTCCTTGGTCCTGGCTGAGAGAGGGCCCCACGGCCAGCACTGCTGACCCTGCCCTGGGCTCCAGTGATGCTGCTGGCCTGGACAAGCCCCTCCGTTCACCTGGGGCCTCTCCTCCTCCCTCGTTCTACTGCCT*CGCCCCTCCCGGGTTCCCAAAGCAGAGGGCGTGGGGGAAAAGAAAAAAGATCCTCTCTCGCTAATCTCCGCCCACCGGCCCTTTAT	---/intergenic

Originally posted by @pkerbs in https://github.com/ndaniel/fusioncatcher/issues/169#issuecomment-1167353883

[pkerbs]

Hey Daniel, this bug seems to be not only restricted to certain genes. Reported fusion events that have "SPOTLIGHT" in the "Fusion_finding_method" column all show wrong positions for the 3' prime partner gene. Moreover, the reported position number (ignoring the chromosome) of the 3' prime gene is close to the reported position number of the 5' gene (ignoring the chromosome). Here are some examples from samples of the LL-100 panel:

With SPOTLIGHT:

sample	gene1	gene2	Fusion_description	Counts_of_common_mapping_reads	Spanning_pairs	Spanning_unique_reads	Longest_anchor_found	Fusion_finding_method	break5prime	break3prime	gene_id1	gene_id2	Exon_1_id(5end_fusion_partner)	Exon_2_id(3end_fusion_partner)	Fusion_sequence	Predicted_effect
697	TCF3	PBX1	known,oncogene,cosmic,chimer2,cgp,ticdb,chimer4kb,chimer4pub,chimer4seq,cancer,tumor,oncokb,mitelman,ccle,t411	24	2342	641	135	BOWTIE+SPOTLIGHT	chr19:1619112:-	chr1:1465091:+	ENSG00000071564	ENSG00000185630			TGCACAACCACGCGGCCCTCCCCAGCCAGCCAGGCACCCTCCCTGACCTGTCTCGGCCTCCCGACTCCTACAGT*GTTTTGAGTATCCGAGGAGCCCAGGAGGAGGAACCCACAGACCCCCAGCTGATGCGGCTGGACAACATGCTGTTAGCGGAAGGCGTGGCGGGGCCTGAGAA	CDS(truncated)/intergenic
DND-41	TAF15	TCF3	known,oncogene,ambiguous,fragments,cancer,tumor,t1	165	5	4	114	BOWTIE+SPOTLIGHT	chr17:35820075:+	chr19:35874574:-	ENSG00000270647	ENSG00000071564			GGGGGTGAGCAGCAAAGTTATTCTACCTATGGAAATCCAGGCAGCCAAGGCTATGGACAAGCATCACAA*GCAAGAGCGGTGAGCGGGGCGCCTATGCCTCCTTCGGGAGAGACGCAGGCGTGGGCGGCCTGACTCAGGCTGGCTTCCTGTCAGGCGAGCTGGCCCTCAACAGCCCCGGGCCCC	CDS(truncated)/intergenic
REC-1	IGKV3-11	CCND1	known,oncogene,chimer2,fragments,cancer,tumor,m0,multi,mitelman	0	3	2	118	BOWTIE+SPOTLIGHT	chr2:89027386:-	chr11:89020700:+	ENSG00000241351	ENSG00000110092			GGAAGCCCCAGCTCAGCTTCTCTTCCTCCTGCTACTCTGGCTCCCAGATACCACCGGAGAAATTGTGTTGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCTCTCCTGCA*ATGACGGCCGAGAAGCTGTGCATCTACACCGACAACTCCATCCGGCCCGAGGAGCTGCTGCAAATGGAG	CDS(truncated)/intergenic
RI-1	MBD3	TCF3	known,oncogene,fragments,cancer,tumor,ccle,t1,10K<gap<100K,short_repeats,sr1.92	16	5	4	108	BOWTIE+SPOTLIGHT	chr19:1592620:-	chr19:1541154:-	ENSG00000071655	ENSG00000071564			CCGGGCGGCGGCGGCGGGCCCGGCGGCGGGCCGAGGAGCCGGGCGCAATGGAGCGGAAG*AGGGTTTCCAGGCCTGAGGTGCCCGCCCTGGCCCCAGGAGAATGAACCAGCCGCAGAGGATGGCGCCTGTGGGCACAGACAAGGAGCTCAGTGACCTCCTGGACTTCAGCATGATGTTCCCGCTGCCTGTCACCAA	CDS(truncated)/intergenic
SEM	PAN3	FLT3	known,oncogene,tcga,chimer4seq,cancer,tumor,tcga-cancer,tcga2,mitelman,ccle,tcga3,reciprocal	0	16	3	103	BOWTIE+SPOTLIGHT	chr13:28261455:+	chr13:28210807:-	ENSG00000152520	ENSG00000122025			AGCTGATCAACAGACATTTAATAACAATGGCTCAAATTGATCAAGCAGATATGC*CAGAAAAAGCAGACAGCTCTGAAAGAGAGGCACTCATGTCAGAACTCAAGATGATGACCCAGCTGGGAAGCCACGAGAATATTGTGAACCTGCTGGGGGCGTGCACACTGTCAG	CDS(truncated)/intergenic

Without Spotlight:

sample	gene1	gene2	Fusion_description	Counts_of_common_mapping_reads	Spanning_pairs	Spanning_unique_reads	Longest_anchor_found	Fusion_finding_method	break5prime	break3prime	gene_id1	gene_id2	Exon_1_id(5end_fusion_partner)	Exon_2_id(3end_fusion_partner)	Fusion_sequence	Predicted_effect
697	RP1-29K1.7	IGH@	lncrna,m11	0	19	4	34	BOWTIE+STAR	chr6:28491647:+	chr14:106591638:-	ENSG00000286819	ENSG09000001017			TGCTTCAGTGGTCACACTCCTAGTCCGCCTTCATGTTCCATCCTGTACAC*CTGGCTCTGCCTTCTAGATAGCAGTAGCAAATCAGTGAAAGTACTAACAG	exonic(no-known-CDS)/---
BC-3	IGH@	NBEA	t8,reciprocal	0	11	3	28	BOWTIE+BLAT	chr14:106453527:-	chr13:35110810:+	ENSG09000001017	ENSG00000172915			CCTGTCTCCTGGCTTCACTGCCTCAGCCTCCCGAGTAGCTGGGATTACAG*GTTCAGCTTTCCCTATACACATATTTGTCTGCTGAATTTATTGGAACTGC	---/CDS(truncated)
BC-3	IGH@	NBEA	t8,reciprocal	0	11	2	23	BOWTIE+STAR	chr14:106589130:-	chr13:35110808:+	ENSG09000001017	ENSG00000172915			CCGGGTTCAAGCGATTCTCCTGCCTCGGCCTCCCGAGTAGCTGGGATTAC*AGGTTCAGCTTTCCCTATACACATATTTGTCTGCTGAATTTATTGGAACT	---/intronic
BC-3	NBEA	IGH@	t8,reciprocal	0	11	14	38	BOWTIE+STAR	chr13:35110978:+	chr14:106533871:-	ENSG00000172915	ENSG09000001017			CTGGGTTATTAATCCTGCTGACAGTAGTGGCATTACACCTAAAGGATTAG*CCAAAGATTCCTGAAGACAGAGCTGATGTGACGTACTCATAGGTGGATCT	CDS(truncated)/---
BC-3	NBEAP1	IGH@	known,pseudogene,chimer2,fragments,cancer,m0,multi	0	3	2	34	BOWTIE+STAR	chr15:20656183:-	chr14:106429433:+	ENSG00000258590	ENSG09000000016			GTTTCTGAAGATGAGAGGCCCACCTTAAATTTCAAAAATAGATCATTTCT*AAAACAAATAACCCCATCAAAAAGTGGGCAAAGGACATGAACAGACACTT	intergenic/---
BCBL-1	IGH@	CLEC2D	banned,known,hpa,m12,t4	0	13	9	41	BOWTIE+STAR	chr14:106438593:+	chr12:9697544:+	ENSG09000000016	ENSG00000069493			CTCTGAAGGCTGTGAGACCCCTGATTTCCCACTTCACACCTCTATATTTC*TGTGTGTGTCTTTAGTTCCTCTGGCGCTGCTGGGTTAGGATCTACCCGAC	---/UTR

So I think there is just a bug in the context of SPOTLIGHT reported fusion events and only the positions of the 3' partners are reported wrongly. Would be nice if you could fix this :) Thank you in advance.

Best wishes, Paul