Table 1 HAPMs significantly associated with the HP phenotype of H5 and H7 virus subtypes.

HAPM	Segment	HP clusters	Num. HP clusters	H7 numbering	References^a	λ [95% CI]	P value	Significance^b
H7NX
R355K^c	PB2	C5 and C6	2		⁵⁸	11.0 [6.8−16.7]	<0.0001	**
A143T^c	HA	C2, C5, C6, C7 and C8	5	125	^{38, 68,69,70}	7.1 [3.3, 13.2]	<0.0001	**
V480I	PB2	C5 and C6	2			8.5 [5.2−13.2]	<0.0001	**
M/L274I	HA	C4 and C8	2	256		6.2 [3.1, 11.5]	0.0024	**
S152L	PB1	C6 and C9	2			5.4 [3.4−8.2]	0.0045	**
V438I	HA	C3 and C8	2	423		4.6 [2.4, 8.3]	0.0093	*
D384N	HA	C6 and C8	2	369		5.1 [2.6, 9.5]	0.018	*
H5NX
V113I	PB1	C2, C4 and C8	3			2.6 [1.6−4.5]	0.0022	**
K379R	HA	C1 and C8	2	363		14.8 [7.4, 27.5]	0.0040	**
M242I	HA	C1 and C8	2	226	⁷³	7.4 [3.7, 13.7]	0.0048	**
S145L/del^d	HA	C5 and C8	2	129	^{38, 63}	See footnote	0.0059	*
A674T	PB2	C2 and C6	2		⁶⁶	5.8 [3.6−9.1]	0.0060	*
N154I/L/Q^{c, e}	HA	C6, C7 and C8	3	138	⁶⁰	See footnote	0.022	*
F127L^c	HA	C3, C7 and C8	3	111	⁶⁰	6.5 [3.3, 12]	0.025	*
I167T	HA	C6 and C8	2	151	⁶²	5.8 [3.0, 10.4]	0.026	*
T204I	HA	C2 and C8	2	188		2.7 [1.4, 4.7]	0.028	*
E627K	PB2	C1 and C8	2			2.9 [1.8−4.6]	0.038	*

^aWhere such HAPMs had been previously mentioned.
^b‘*’ indicates a p value < 0.05, whilst ‘**’ indicates a p value < 0.01.
^cScored as positively selected site under different methods (see Supplementary Table 1 in the Supplementary Information).
^dIndividual lambda values for each site are as follows: for 145 L 77.5 [69.5, 100.0] with a p value of 0.00, and for 145del 7.0 [0.5, 14.7] with a p value of 0.04.
^eIndividual lambda values for each site are as follows: for 154I 1.7 [1.0, 2.7], for 154 L 3.2 [1.9, 5.2] and for 154Q: 3.4 [2.0, 5.8], all with a p value of 0.00.

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