Identification of positive selection in genes is greatly improved by using experimentally informed site-specific models

Table 3 At most sites of selection identified using ExpCM, mutations affect drug resistance or immune escape

Gene	Site	Affects biologically relevant phenotype?
β-lactamase	35	No evidence implicating this site in resistance [15]
	48	No evidence implicating this site in resistance [15]
	104	E104K involved in β-lactam resistance [15]
	112	No evidence implicating this site in resistance [15]
	164	R164C, R164H, and R164S involved in β-lactam resistance [15]
	182	M182T potentiates resistance [15]
	238	G238S involved in β-lactam resistance [15]
	240	E240K involved in β-lactam resistance [15]
	244	R244C, R244H, and R244S involved in inhibitor resistance [15]
NP	20	In a T-cell epitope [94]
	101	In an antibody epitope [95]
	105	In a T-cell epitope [96]
	131	Not part of known immune epitope
	290	In an antibody epitope [97]
	319	Not part of known immune epitope
	371	In an antibody epitope [98, 99]
	375	E375G interacts with T-cell escape mutation at 384 [58, 100]
	384	R384G and R384K are T-cell escape mutations [38, 100]
	422	K422R is a T-cell escape mutation [101]
HA	138	Contacts antigenic-site residues defined by the experiments of [40]
	189	Contacts antigenic-site residues defined by the experiments of [40]
	225	An antigenic site residue defined by the experiments of [40]; also affects receptor-binding specificity and so known to undergo substitutions both during host adaptation and viral passaging in the lab [84–87]

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