Figure 3
Figure 3. Graphical representation of the Grubbs test for outliers results on gene integration frequencies in ∼ 10-20 Mb genomic regions around CIS. The y-axis is the ratio Z that measures how distant is the integration frequency of a given gene with respect to the average of all genes analyzed (genes targeted by ≥ 1 integration contained within the specified genomic interval). The x-axis is the chromosomal position of the gene (coordinates in base pairs). A negative or positive ratio Z value implies that the gene is targeted at a frequency below or above the average, respectively. The red lines indicate the threshold beyond which the values can be considered significantly different. The red triangles indicate genes considered as CISs in previous publications with the use of the classic statistical approach (in parentheses the number of integrations targeting each gene). (A) Two examples of ratio Z of gene integration frequency at genomic regions around CISs from γRV-based X-SCID and CGD clinical trials. LMO2 (targeted by 7 integrations) and CCND2 (7 integrations) appear to be targeted at a significantly higher frequency by this test (see supplemental Statistical Material for analyses of other CISs from the same clinical trials). (B) Ratio Z of gene integration frequency at the genomic region around Braf (68 integrations) and the neighboring genes in histiocytic sarcomas form Cdkn2a−/− mice injected with LV.SF.LTR. (C) A very similar integration profile is found at Braf (24 integrations) in sarcomas from Arf−/− SB transposon/transposase transgenic mice. (D) Ratio Z representation of 2 genomic regions at LV CISs in common between the ALD clinical trial and the hematochimeric model show that none of the identified CISs is a significant outlier.

Graphical representation of the Grubbs test for outliers results on gene integration frequencies in ∼ 10-20 Mb genomic regions around CIS. The y-axis is the ratio Z that measures how distant is the integration frequency of a given gene with respect to the average of all genes analyzed (genes targeted by ≥ 1 integration contained within the specified genomic interval). The x-axis is the chromosomal position of the gene (coordinates in base pairs). A negative or positive ratio Z value implies that the gene is targeted at a frequency below or above the average, respectively. The red lines indicate the threshold beyond which the values can be considered significantly different. The red triangles indicate genes considered as CISs in previous publications with the use of the classic statistical approach (in parentheses the number of integrations targeting each gene). (A) Two examples of ratio Z of gene integration frequency at genomic regions around CISs from γRV-based X-SCID and CGD clinical trials. LMO2 (targeted by 7 integrations) and CCND2 (7 integrations) appear to be targeted at a significantly higher frequency by this test (see supplemental Statistical Material for analyses of other CISs from the same clinical trials). (B) Ratio Z of gene integration frequency at the genomic region around Braf (68 integrations) and the neighboring genes in histiocytic sarcomas form Cdkn2a−/− mice injected with LV.SF.LTR. (C) A very similar integration profile is found at Braf (24 integrations) in sarcomas from Arf−/− SB transposon/transposase transgenic mice. (D) Ratio Z representation of 2 genomic regions at LV CISs in common between the ALD clinical trial and the hematochimeric model show that none of the identified CISs is a significant outlier.

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