About Sequence's Omega value: Either E/K or O/X

[agdiaz]

Hello dear localCIDER contributors,
How are you? I hope you are all doing well.

I would like to ask you a question related to Omega metric. The main function to get it is:

• E
• K

localCIDER/localcider/backend/sequence.py

Lines 443 to 467 in 6eea6b5

	def Omega(self):
	"""
	Return the Omega value, as defined in Martin et al. [1]
	[1] Martin, E.W., Holehouse, A.S., Grace, C.R., Hughes, A., Pappu, R.V., and
	Mittag, T. (2016). Sequence determinants of the conformational properties
	of an intrinsically disordered protein prior to and upon multisite phosphorylation.
	J. Am. Chem. Soc. (10.1021/jacs.6b10272)
	"""
	# firstly convert the sequence into a 2 letter alphabet of
	# E/D/R/K/P or 'other'
	newseq=''
	for res in self.seq:
	if res == 'P' or res =='E' or res =='D' or res =='K' or res =='R':
	newseq=newseq+'E'
	else:
	newseq=newseq+'K'
	# then calculate the new kappa value in this new sequence space and
	# return the value
	augmented_seq = Sequence(newseq)
	return augmented_seq.kappa()

While the method to return the omega sequence does a different character replacing rule:

• X
• O

localCIDER/localcider/backend/sequence.py

Lines 471 to 487 in 6eea6b5

	def Omega_seq(self):
	"""
	Return the Omega sequence, where R/K/D/E/P are X and all other residues
	are O. This is useful for visualizing what the sequence used to calculate
	Omega actually looks like.
	"""
	# firstly convert the sequence into a 2 letter alphabet of
	# E/D/R/K/P or 'other'
	newseq=''
	for res in self.seq:
	if res == 'P' or res =='E' or res =='D' or res =='K' or res =='R':
	newseq=newseq+'X'
	else:
	newseq=newseq+'O'
	return newseq

I wonder if they should have the same set of replacing rules ?
Thank you in advance for your answer

[alexholehouse]

Thanks for your question! No 😄!

The Omega() function (top) projects the sequence into a binary-alphabet space where the characters in that space are E and K, and then because E and K are charged, we can use the original kappa implementation to calculate the patterning in the binary space.

The Omega_seq() function is - in contrast - solely for visualization to make it possible to see where residues fall into the two classes. We choose O and X because these are not canonical amino acid letters, so there is no risk of confusing the so-called omega-seq with an actual amino acid sequence. If we used E/K here we'd generate a 'charged amino acid sequence' which is not the point of the function.