A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell transplantation

Paul, Dirk S.; Jones, Allison; Sellar, Rob S.; Mayor, Neema P.; Feber, Andrew; Webster, Amy P.; Afonso, Neuza; Sergeant, Ruhena; Szydlo, Richard M.; Apperley, Jane F.; Widschwendter, Martin; Mackinnon, Stephen; Marsh, Steven G. E.; Madrigal, J. Alejandro; Rakyan, Vardhman K.; Peggs, Karl S.; Beck, Stephan

doi:10.1186/s13073-015-0246-z

Table 2 Significant DMPs associated with aGVHD severity status

From: A donor-specific epigenetic classifier for acute graft-versus-host disease severity in hematopoietic stem cell transplantation

Rank	DMP	Adj. P value	Δβ-value	Chr.	Position	Gene	Feature	CpG context	LOOCV
1	cg20475486	1.38 × 10⁻³	−0.180	14	70,317,075	–	IGR	Island	85
2	cg10399005	1.62 × 10⁻⁴	−0.162	14	70,316,898	–	IGR	Island	85
3	cg16925210	1.60 × 10⁻⁵	0.130	2	216,946,718	PECR	TSS200	Island	85
4	cg00762468	7.61 × 10⁻⁶	0.066	16	103,568	POLR3K	1stExon	Island	85
5	cg26758857	1.07 × 10⁻⁷	−0.062	22	36,649,135	APOL1	5′UTR	–	85
6	cg21752471	8.92 × 10⁻⁴	−0.061	5	133,861,794	PHF15	TSS200	Island	85
7	cg21459486	5.14 × 10⁻⁴	−0.060	13	112,885,426	–	IGR	–	85
8	cg16495818	2.05 × 10⁻⁵	−0.055	11	73,306,367	FAM168A	5′UTR	Shelf	85
9	cg16276523	5.29 × 10⁻⁴	−0.094	1	161,049,579	PVRL4	Body	Island	84
10	cg19558933	5.11 × 10⁻³	−0.129	11	134,632,242	–	IGR	Island	82
11	cg00087067	9.63 × 10⁻³	0.071	5	5,265,509	ADAMTS16	Body	–	82
12	cg14099595	1.62 × 10⁻²	0.067	5	145,717,283	POU4F3	TSS1500	Shore	82
13	cg07464977	6.69 × 10⁻³	−0.062	5	2,097,136	–	IGR	–	82
14	cg11364888	8.50 × 10⁻³	−0.055	12	116,920,304	–	IGR	–	82
15	cg24599107	9.57 × 10⁻³	−0.073	1	161,049,443	PVRL4	Body	Island	81
16	cg07280807	8.94 × 10⁻³	−0.151	14	70,317,239	–	IGR	Island	80
17	cg14546466	2.49 × 10⁻²	−0.077	2	11,796,974	–	IGR	Island	80
18	cg03481039	8.60 × 10⁻³	−0.065	11	116,662,012	APOA5	Body	Shore	80
19	cg03896685	2.62 × 10⁻²	−0.062	7	65,512,561	–	IGR	Shelf	80
20	cg00245850	1.78 × 10⁻²	0.060	8	143,925,513	GML	Body	–	80
21	cg09284655	1.17 × 10⁻²	−0.152	14	70,317,228	–	IGR	Island	79
22	cg10287485	2.20 × 10⁻²	0.090	11	69,473,145	–	IGR	Shelf	79
23	cg19704238	1.55 × 10⁻²	0.058	10	85,900,022	GHITM	5′UTR	Shore	79
24	cg09282654	3.33 × 10⁻²	0.070	7	123,563,992	SPAM1	TSS1500	–	75
25	cg16701890	3.57 × 10⁻²	0.064	2	119,906,008	–	IGR	–	73
26	cg04664342	3.80 × 10⁻²	−0.107	17	4,685,905	TM4SF5	Body	Island	65
27	cg20307347	4.06 × 10⁻²	−0.119	2	231,734,563	ITM2C	Body	Shelf	58
28	cg19311448	4.17 × 10⁻²	−0.075	2	11,797,017	–	IGR	Island	45
29	cg09852744	4.55 × 10⁻²	0.058	6	158,732,256	TULP4	TSS1500	–	39
30	cg16398628	4.46 × 10⁻²	0.090	10	91,011,689	LIPA	TSS200	Island	32
31	cg20585841	4.57 × 10⁻²	−0.164	8	102,729,926	NCALD	Body	–	21

DMPs achieving a P value <0.05 after Bonferroni correction and a DNA methylation difference of at least ±5 % are reported. DMPs are ranked according to their recurrence in the LOOCV, for which a total of 85 iterations were performed, and their absolute DNA methylation difference. DNA methylation differences were calculated as follows: mean β-values of HSCT donors matched to recipients with severe aGVHD – mean β-values of HSCT donors matched to recipients with no/mild aGVHD. The four highlighted DMPs on chromosome 14q24.2 form a region with consistent DNA hypomethylation in graft donors matched to recipients with severe aGVHD compared to donors paired with recipients with no/mild aGVHD (Fig. 2a). Chromosomal positions are reported in genome build = hg19

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ISSN: 1756-994X

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