Evaluation of pediatric epigenetic clocks across multiple tissues

Clinical Epigenetics

Table 2 Performance comparison of epigenetic clocks in ECHO datasets

Tissue	Array	Birth term	GA (weeks)	N	Knight				Bohlin
Tissue	Array	Birth term	GA (weeks)	N	\(r\)*	Median error^†	Median res^§	Mean diff^‡	\(r\)*	Median error^†	Median res^§	Mean diff^‡
Gestational age (weeks) estimation
Blood spot	450K	Term	39.36 ± 1.91	253	0.35	1.11	0.96	− 0.08	0.47	1.02	0.52	− 0.94
	EPIC	Term	38.73 ± 1.60	176	0.48	0.89	0.91	− 0.32	0.65	1.42	0.43	− 1.35
	EPIC	Preterm	25.65 ± 1.27	272	0.57	2.52	1.01	2.52	0.67	3.91	0.51	4.01
CBMC	EPIC	Term	38.98 ± 1.39	142	0.38	2.02	0.83	− 1.90	0.66	1.73	0.35	− 1.56
Cord blood	27K	Term	39.00 ± 1.29	159	0.31	1.10	0.97	− 0.39	0.37	0.58	0.14	− 0.31
	450K	Term	39.19 ± 1.43	1194	0.41	0.98	0.82	− 0.45	0.57	1.10	0.46	− 0.99
	EPIC	Term	38.92 ± 1.74	585	0.34	1.11	0.91	− 0.49	0.55	1.64	0.52	− 1.41

Tissue	Array	Birth term	GA (weeks)	N	Lee				Mayne
Tissue	Array	Birth term	GA (weeks)	N	\(r\)*	Median error^†	Median res^§	Mean diff^‡	\(r\)*	Median error^†	Median res^§	Mean diff^‡
Placental gestational age (weeks) estimation
Placenta	450K	Term	38.98 ± 1.15	59	0.5	0.60	0.52	− 0.11	0.27	1.55	0.83	− 1.62
	EPIC	Term	38.79 ± 1.18	121	0.36	0.88	0.76	− 0.32	− 0.05	2.11	1.37	0.92
		Preterm	25.68 ± 1.25	399	0.6	2.50	0.93	2.59	0.35	7.27	1.22	7.38

Tissue	Array	Birth term	Age (days)	N	Horvath				PedBE
Tissue	Array	Birth term	Age (days)	N	\(r\)*	Median error^†	Median res^§	Mean diff^‡	\(r\)*	Median error^†	Median res^§	Mean diff^‡
Pediatric chronological age (years) estimation
Buccal cells	EPIC	Term	3.62 ± 5.24	72	− 0.36	0.98	0.17	1.00	0.12	0.05	0.05	0.04
		Preterm	84.95 ± 31.64	480	0.41	1.15	0.34	1.26	0.62	0.09	0.09	0.07
PBMC	450K	Term	4044.20 ± 1098.28	150	0.79	1.72	1.26	− 1.33	0.78	6.73	0.26	− 5.29
	EPIC	Term	2555	140	NA	3.48	1.24	3.48	NA	0.83	0.38	− 0.72
Peripheral whole blood	450K	Term	2504.60 ± 705.79	307	0.68	0.85	0.86	0.30	0.56	1.73	0.30	− 1.07
	EPIC	Term	153 ± 93.44	46	0.74	1.50	0.29	1.49	0.68	4.09	0.18	4.09

*Spearman correlation between predicted epigenetic age and observed gestational age/chronological age
^†Median of the absolute difference between the predicted age and the observed age (weeks for gestational age and years for chronological age)
^§Median of the absolute residuals from regressing the predicted epigenetic age onto the observed age (weeks for gestational age and years for chronological age)
^‡Mean of the signed difference between the predicted age and the observed age (weeks for gestational age and years for chronological age).
CBMC: Cord blood mononuclear cells, GA: gestational age, PBMC: Peripheral blood mononuclear cells

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