Homozygous LOF Burden

Tally caller-annotated homozygous loss-of-function variants per gene.

Description

Homozygous alternate variants with a supplied loss-of-function annotation can be tallied by gene.

Homozygous alternate variants with a supplied loss-of-function annotation can be tallied by gene. Annotation and genotype interpretation determine the input category.

Tally caller-annotated homozygous loss-of-function variants per gene.

When to use Homozygous LOF Burden

Use this for the following task: Tally caller-annotated homozygous loss-of-function variants per gene.

Prepare the caller-filtered sequences, counts, coordinates or annotations requested below. Keep identifiers and paired lists aligned on the same reference.

How to use Homozygous LOF Burden and understand its results

Prepare the caller-filtered sequences, counts, coordinates or annotations requested below. Keep identifiers and paired lists aligned on the same reference.
Enter geneIds, alternateAlleleCounts, lossOfFunctionFlags using the field table, then run the tool.
Read burdenGenes, homozygousLofCounts, totalHomozygousLof. Interpret flags, units, ordering and placeholder values using the rules below.
Review any reported issue or failed check, correct the supplied values when appropriate, and verify the result in its intended context.

Input field	Meaning	Value type and bounds	Requirement
geneIds	Gene ids	list of string; minimum entries 1; maximum entries 100000; each entry: string; minimum text length 1; maximum text length 1000000; pattern \S	Required
alternateAlleleCounts	Alternate allele counts	list of integer; minimum entries 1; maximum entries 100000; each entry: integer; minimum 0; maximum 2	Required
lossOfFunctionFlags	Loss of function flags	list of integer; minimum entries 1; maximum entries 100000; each entry: integer; minimum 0; maximum 1	Required

Align gene IDs, supported dosages and numeric annotation flags. Tally qualifying records by exact gene ID, sort gene keys lexically and sum their counts.^[1]

count per gene where alternateAlleleCount == 2 AND lossOfFunctionFlag == 1

This summarizes the declared operation. Units, indexing, inclusivity and exceptional cases are explained in the surrounding text.

Output field	Meaning	Value type
burdenGenes	Burden genes	list of string
homozygousLofCounts	Homozygous lof counts	list of integer
totalHomozygousLof	Total homozygous lof	integer

json

{
  "input": {
    "geneIds": [
      "A",
      "A",
      "B"
    ],
    "alternateAlleleCounts": [
      2,
      1,
      2
    ],
    "lossOfFunctionFlags": [
      1,
      1,
      0
    ]
  },
  "output": {
    "burdenGenes": [
      "A"
    ],
    "homozygousLofCounts": [
      1
    ],
    "totalHomozygousLof": 1
  }
}

Limitations and assumptions

Repeated records count separately. The tool does not annotate variants, validate transcript consequence or infer disease.

The tool operates on supplied local data; alignment, filtering and annotation must already be appropriate for the stated calculation. Malformed requests produce input errors. A successfully evaluated request can still contain false flags, empty result lists or a result outside the supplied threshold; those outcomes have the meanings stated above.

Alternative or Complementary methods

Choose Trans Heterozygote Pairs for this operation: Find known trans-phased heterozygous variant pairs within each gene; not a pathogenicity classification. For a complementary task, use Private Singleton Tally for this operation: Identify alternate alleles seen exactly once in the target and absent from all other samples.

The implementation reference documents the exact calculation, supported input shapes and returned fields.

References

Homozygous LOF Burden — tool.io

Similar or alternative tools

Trans Heterozygote Pairs
Find known trans-phased heterozygous variant pairs within each gene; not a pathogenicity classification.
Private Singleton Tally
Identify alternate alleles seen exactly once in the target and absent from all other samples.