This article outlines the default positional liabilities for numbered antibody sequences, as well as how to specify your own custom positional liabilities. The positional liabilities work for all supported numbering schemes: IMGT, Kabat, Chothia, Martin and AHo. If you'd like to know more about numbering schemes please see our main article: Numbering Schemes. If you would like to know more about other kinds of default liabilities, see Antibody Sequence Liabilities.
Jump to:
- List of default position-based liabilities
- General rules for specifying positional liabilities
- Saving different sets of liabilities for different datasets
- What are the positional liabilities based on?
List of default position-based liabilities
-10 Liability (Medium):
# Positional residues heavy or light chain:
Position ![S T] !position_found (IMGT-22 AHo-22 H-KabatBased-21 L-KabatBased-22)
Position !C !position_found (IMGT-23 AHo-23 H-KabatBased-22 L-KabatBased-23)
Position !W !position_found (IMGT-41 AHo-43 H-KabatBased-36 L-KabatBased-35)
Position !C !position_found (IMGT-104 AHo-106 H-KabatBased-92 L-KabatBased-88)
Position !G !position_found (IMGT-119 AHo-140 H-KabatBased-104 L-KabatBased-99)
Position !G !position_found (IMGT-121 AHo-142 H-KabatBased-106 L-KabatBased-101)
# Positional residues light chain only:
Position ![Q L] !position_found (L-IMGT-43 L-AHo-45 L-KabatBased-37)
Position !G !position_found (L-IMGT-70 L-AHo-73 L-KabatBased-57)
Position ![V I] !position_found (L-IMGT-71 L-AHo-74 L-KabatBased-58)
Position ![P S] !position_found (L-IMGT-72 L-AHo-75 L-KabatBased-59)
Position !F !position_found (L-IMGT-118 L-AHo-139 L-KabatBased-98)
# Positional residues heavy chain only:
Position !G !position_found (H-IMGT-27 H-AHo-27 H-KabatBased-26)
Position ![Y F G] !position_found (H-IMGT-28 H-AHo-29 H-KabatBased-27)
Position ![V I A] !position_found (H-IMGT-42 H-AHo-44 H-KabatBased-37)
Position ![R K] !position_found (H-IMGT-43 H-AHo-45 H-KabatBased-38)
Position !Q !position_found (H-IMGT-44 H-AHo-46 H-KabatBased-39)
Position ![G A S] !position_found (H-IMGT-54 H-AHo-56 H-KabatBased-49)
Position ![L I V F T A] !position_found (H-IMGT-76 H-AHo-78 H-KabatBased-67)
Position ![T S I A] !position_found (H-IMGT-77 H-AHo-79 H-KabatBased-68)
Position !W !position_found (H-IMGT-118 H-AHo-139 H-KabatBased-103)
Position !Q !position_found (H-IMGT-120 H-AHo-141 H-KabatBased-105)
Liability (Low):
# Positional residues light chain only:
Position ![Y L F] !position_found (L-IMGT-42 L-AHo-44 L-KabatBased-36)
Position ![I V] !position_found (L-IMGT-54 L-AHo-56 L-KabatBased-48)
Position ![Y K F] !position_found (L-IMGT-55 L-AHo-57 L-KabatBased-49)
# Positional residues heavy chain only:
Position !S !position_found (H-IMGT-26 H-AHo-26 H-KabatBased-25)
Position !W !position_found (H-IMGT-52 H-AHo-54 H-KabatBased-47)
Position ![R K] !position_found (H-IMGT-75 H-AHo-77 H-KabatBased-66)
Position !A !position_found (H-IMGT-105 H-AHo-107 H-KabatBased-93)
Position !R !position_found (H-IMGT-106 H-AHo-108 H-KabatBased-94)
General Rules for Specifying Positional Liabilities
The default liabilities above all perform two checks:
1. Does the position exist? (ie. can it be numbered at this point)
2. Is the residue at that position the amino acid(s) we are expecting?
It then applies a score change (either positive or negative) if the liability is found.
Take the below example from our defaults:
-10 Liability (Medium):
Position !W !position_found (IMGT-41 AHo-43 H-KabatBased-36 L-KabatBased-35)
-
-10 Liability (Medium):
- This specifies that if the requirements of the liability are found, -10 will be added to the overall "score" of the antibody sequence. Note: Positive values can be used.
-
Position !W
- This refers to a tryptophan not being found at the specified position.
- Without the ! signifier, the liability would exist only if a tryptophan was found at the specified position
- Additional amino acids can be specified in square brackets eg. ![Y L F]
- This refers to a tryptophan not being found at the specified position.
-
!position_found
- This refers to whether the position (number) exists at all
- (IMGT-41 AHo-43 H-KabatBased-36 L-KabatBased-35)
- The position is specified as residue 41 for IMGT, 43 for AHo and residue 36 for Kabat-numbered heavy chains an 35 for Kabat-numbered light chains.
- The position is specified as residue 41 for IMGT, 43 for AHo and residue 36 for Kabat-numbered heavy chains an 35 for Kabat-numbered light chains.
In the image below, we can see this liability for !W found in a sequence numbered with AHo:
- The column Liability (Medium) contains other kinds of non-positional liabilities as well, such as hydrolysis (NP motif). These other liabilities can be found in our main article: Antibody Sequence Liabilities.
- The column Position contains only the positional liabilities where an amino acid has changed from what is expected by the liability.
- This is displayed as a count of how many amino acids were different from expected, followed by their position (eg. Heavy-AHo-43)
- The column Position (Not Found) calls any numbers/positions that could not be found, ie. does the position exist. We can see that position 107 for AHo could not be found/numbered in the first sequence.
- This is also displayed as a count of how many positions did not exist, followed by the position(s) themselves.
- On the sequence itself, annotations are present for the liability. Highlighted on the sequence is a !W annotation at position 43.
Note: In the above image, all the cases of !W (Not a tryptophan) at position AHo-43 were found using the following filter:
['Liability (Medium)'] LIKE '%!W (Position, Heavy-AHo-43)%'
If you would like to learn more about filtering syntax, please see our main article: Filtering your sequences.
Examples of Positional Liabilities/Assets
1. A Positional Asset
+10 Conserved Residue:
Position Y !position_found (AHo-109)
The above example will add +10 points to the overall score of a sequence if a tyrosine is found at position 109 (when using the AHo numbering scheme).
Below we can see that a new column is present called Conserved Residue, and that on the sequence the Y has been annotated at position 109.
2. A Liability for "Position Found" only
-1 Missing Position:
Missing !position_found (AHo-29)
The above example will add -1 points to the score of any antibody sequence where the numbered position 29 (AHo) could not be found.
It will also generate a new column called Missing Position that will track any numbers not found. Annotations for missing numbers will be present on the sequence, at the start of the stretch of missing numbers.
Saving different sets of liabilities for different datasets
Geneious Biologics allows you to save Profiles which can be used to record and re-run alternative settings depending on the dataset. This means that you can specify different Antibody Sequence Liabilities and other settings depending on what dataset you are working with.
Profiles can be saved and applied at the bottom of our Annotation analysis pipelines:
What are the positional liabilities based on?
Our default positional liabilities represent highly conserved residues in the Human Ig germline genes. As such, they are less applicable to the heavy and light chains of other species. Saving alternate Profiles (see the section above) can allow you to develop your own liability settings depending on the reference database used, or type of analysis.