TABLE 2.

Sequence covariation analysis

Covariation and aa positiona	MA 2 aa positionb	Z scorec	JI score derived fromd:		SE	Mutation occurrence as determined frome:
			Sequence data	Random model		Sequence data			Random model
						XY	XO	YO	XY	XO	YO
Matrix-matrix (MA 1)
76	79	39.05	0.300	0.269	0.001	134	218	94	899	1,533	916
76	81	61.20	0.081	0.048	0.001	29	323	6	124	2,308	165
79	81	47.84	0.087	0.054	0.001	21	207	14	108	1,707	181
Protease-matrix (PR 1)
54	79	12.71	0.046	0.040	0.001	11	10	217	77	125	1,738
54	81	57.49	0.120	0.019	0.002	6	15	29	9	193	280
90	76	5.05	0.039	0.037	0.000	14	11	338	93	106	2,339
90	79	22.03	0.050	0.038	0.001	12	13	216	74	125	1,741
90	81	52.46	0.111	0.025	0.002	6	19	29	12	187	277

^aMA 1, matrix mutation position 1; PR 1, protease mutation position 1.

^bMA 2, matrix mutation position 2.

^cZ score: (sequence data JI score − random model JI score)/sequence data JI score SE. The greater the value of the Z score, the greater the evidence that two amino acids covary. However, the results shown are all statistically significant based on the magnitude of the Z score compared with a standard normal distribution corrected for multiple testing.

^dJaccard index (JI): JI = XY/XY + XO + YO. Shown are the JI scores calculated from both sequence data and the random data model.

^eFor mutation occurrence, XY represents the occurrence of mutations 1 and 2 in the same sequence, XO represents the number of sequences with mutation 1 alone, and YO represents the number of sequences with mutation 2 alone.