Table 1. List of variables.

Symbol	Definition
L	Total number of column pairs in the ICA array
r	Maximum 3D distance used to define contacting residue pairs (default: 5 Å)
D	Number of contacting pairs, i.e. distinguished elements
X	Optimum cut point (as defined by the ICA algorithm) for partitioning an array of length L
d	Number of left-distinguished elements, i.e. contacting pairs to the left of the cut point X (inclusive)
m	Minimum sequence separation between residue pairs in a query protein of known structure
Pa	Estimated p-value for finding d distinguished elements to the left of X in the array
R	The number, among the d elements with smallest pairwise distances, that occur to the left of X (used for calculating Pb)
Pb	The probability, based on the cumulative hypergeometric distribution, of R being at least the value observed
PJ	Estimated joint p-value
S	-log10 P, where P corresponds to PJ after correcting for multiple tests
x	Constant cut point (used instead of an optimized cut point X)
ℓ	The length of the input MSA
F	Numerical factor defining the constant cut point as x = F × ℓ
Px	The probability, based on the cumulative hypergeometric distribution, of d being at least the number observed up to constant cut point x
PF	Estimated joint p-value that combines Pb and Px, where x = F × ℓ
SF	-log10 PF