Limits...
Detection of internal exon deletion with exon Del.

Guo Y, Zhao S, Lehmann BD, Sheng Q, Shaver TM, Stricker TP, Pietenpol JA, Shyr Y - BMC Bioinformatics (2014)

Bottom Line: Such deletions have potentially significant biological meaning, and they are often too short to be considered copy number variation.Further comparisons with multiple sequencing-based CNV tools showed that ExonDel is capable of detecting unique IEDs not found by other CNV tools.ExonDel is an efficient way to screen for novel and known IEDs using exome sequencing data.

View Article: PubMed Central - PubMed

Affiliation: Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, 2220 Pierce Ave, 549 Preston Research Building, Nashville, TN 37232, USA. yan.guo@vanderbilt.edu.

ABSTRACT

Background: Exome sequencing allows researchers to study the human genome in unprecedented detail. Among the many types of variants detectable through exome sequencing, one of the most over looked types of mutation is internal deletion of exons. Internal exon deletions are the absence of consecutive exons in a gene. Such deletions have potentially significant biological meaning, and they are often too short to be considered copy number variation. Therefore, to the need for efficient detection of such deletions using exome sequencing data exists.

Results: We present ExonDel, a tool specially designed to detect homozygous exon deletions efficiently. We tested ExonDel on exome sequencing data generated from 16 breast cancer cell lines and identified both novel and known IEDs. Subsequently, we verified our findings using RNAseq and PCR technologies. Further comparisons with multiple sequencing-based CNV tools showed that ExonDel is capable of detecting unique IEDs not found by other CNV tools.

Conclusions: ExonDel is an efficient way to screen for novel and known IEDs using exome sequencing data. ExonDel and its source code can be downloaded freely at https://github.com/slzhao/ExonDel.

Show MeSH

Related in: MedlinePlus

Comparison between ExonDel and other CNV calling tools.(A) The length distribution of the deletion detected by all tools; (B) The number of deletions detected using all tools at window size 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4288651&req=5

Fig4: Comparison between ExonDel and other CNV calling tools.(A) The length distribution of the deletion detected by all tools; (B) The number of deletions detected using all tools at window size 1.

Mentions: In addition to the multi-exon deletion in NOTCH1, many novel IED candidates were identified, some containing as few as a single exon (Table 1). IEDs with a single exon are more likely to result from sequencing artifacts. For comparative purposes, we screened our samples for CNV using 6 sequencing data-based CNV callers: ExomeCNV [11], CNVnator [12], CoNIFER [13], Control-FREEC [14], ExomeCopy [15] and cn.MOPS [16]. Even after combining results from all six CNV tools, ExonDel can still indentify many novel deletion candidates not identified by other CNV tools (Table 1). Figure 4A demonstrates the distribution of length of deletions detected by each tool. Clearly, ExonDel can identify smaller deletions while other CNV tools identified deletions with long length. Figure 4B shows the number of deletions detected by each tool. At window size 1, a significantly more number of potential IEDs were identified by ExonDel on all 16 samples, given researcher a greater chance at identifying the true biological relevant IDEs. The NOTCH1 deletion we described was identified in 3 out of the 6 tested CNV tools. The detailed results of the ExonDel and CNV comparison can be viewed in Additional file 3: Table S3.Figure 4


Detection of internal exon deletion with exon Del.

Guo Y, Zhao S, Lehmann BD, Sheng Q, Shaver TM, Stricker TP, Pietenpol JA, Shyr Y - BMC Bioinformatics (2014)

Comparison between ExonDel and other CNV calling tools.(A) The length distribution of the deletion detected by all tools; (B) The number of deletions detected using all tools at window size 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4288651&req=5

Fig4: Comparison between ExonDel and other CNV calling tools.(A) The length distribution of the deletion detected by all tools; (B) The number of deletions detected using all tools at window size 1.
Mentions: In addition to the multi-exon deletion in NOTCH1, many novel IED candidates were identified, some containing as few as a single exon (Table 1). IEDs with a single exon are more likely to result from sequencing artifacts. For comparative purposes, we screened our samples for CNV using 6 sequencing data-based CNV callers: ExomeCNV [11], CNVnator [12], CoNIFER [13], Control-FREEC [14], ExomeCopy [15] and cn.MOPS [16]. Even after combining results from all six CNV tools, ExonDel can still indentify many novel deletion candidates not identified by other CNV tools (Table 1). Figure 4A demonstrates the distribution of length of deletions detected by each tool. Clearly, ExonDel can identify smaller deletions while other CNV tools identified deletions with long length. Figure 4B shows the number of deletions detected by each tool. At window size 1, a significantly more number of potential IEDs were identified by ExonDel on all 16 samples, given researcher a greater chance at identifying the true biological relevant IDEs. The NOTCH1 deletion we described was identified in 3 out of the 6 tested CNV tools. The detailed results of the ExonDel and CNV comparison can be viewed in Additional file 3: Table S3.Figure 4

Bottom Line: Such deletions have potentially significant biological meaning, and they are often too short to be considered copy number variation.Further comparisons with multiple sequencing-based CNV tools showed that ExonDel is capable of detecting unique IEDs not found by other CNV tools.ExonDel is an efficient way to screen for novel and known IEDs using exome sequencing data.

View Article: PubMed Central - PubMed

Affiliation: Vanderbilt Ingram Cancer Center, Center for Quantitative Sciences, 2220 Pierce Ave, 549 Preston Research Building, Nashville, TN 37232, USA. yan.guo@vanderbilt.edu.

ABSTRACT

Background: Exome sequencing allows researchers to study the human genome in unprecedented detail. Among the many types of variants detectable through exome sequencing, one of the most over looked types of mutation is internal deletion of exons. Internal exon deletions are the absence of consecutive exons in a gene. Such deletions have potentially significant biological meaning, and they are often too short to be considered copy number variation. Therefore, to the need for efficient detection of such deletions using exome sequencing data exists.

Results: We present ExonDel, a tool specially designed to detect homozygous exon deletions efficiently. We tested ExonDel on exome sequencing data generated from 16 breast cancer cell lines and identified both novel and known IEDs. Subsequently, we verified our findings using RNAseq and PCR technologies. Further comparisons with multiple sequencing-based CNV tools showed that ExonDel is capable of detecting unique IEDs not found by other CNV tools.

Conclusions: ExonDel is an efficient way to screen for novel and known IEDs using exome sequencing data. ExonDel and its source code can be downloaded freely at https://github.com/slzhao/ExonDel.

Show MeSH
Related in: MedlinePlus