Weird ALT call not being treated as ALT

[mbhall88]

I have been looking at the mutation genotype concordance between Illumina and Nanopore and have stumbled across a weird case.

The mutation katG_G1903GCT-C2154209AGC is called as ALT (1/1) in Illumina, but REF (0/0) on Nanopore. However, the ALT call by mykrobe-Illumina does not appear in the susceptibility information for (isoniazid) resistance...

The command to generate the Illumina file was

$ mykrobe predict -e 0.001 -o /hps/nobackup/iqbal/mbhall/tech_wars/analysis/resistance_prediction/results/mykrobe/predict/illumina/south_africa/R25048/R25048.mykrobe.json -i /hps/nobackup/iqbal/mbhall/tech_wars/data/QC/subsampled/south_africa/illumina/R25048/R25048.subsampled.R1.fastq.gz /hps/nobackup/iqbal/mbhall/tech_wars/data/QC/subsampled/south_africa/illumina/R25048/R25048.subsampled.R2.fastq.gz           --force -A --debug --format json --min_proportion_expected_depth 0.20 --sample R25048 --species tb           -t 4 -m 4096MB > /hps/nobackup/iqbal/mbhall/tech_wars/analysis/resistance_prediction/logs/rules/mykrobe/illumina/south_africa/R25048.log 2>&1

Here is the entry from Illumina

            "katG_G1903GCT-C2154209AGC": {
                "variant": "ref-G1903GCT?var_name=C2154209AGC&num_alts=1&ref=NC_000962.3&enum=0&gene=katG&mut=G1903GCT",
                "genotype": [
                    1,
                    1
                ],
                "genotype_likelihoods": [
                    -2855.8461119184817,
                    -99999999,
                    -1465.7537363958886
                ],
                "info": {
                    "coverage": {
                        "reference": {
                            "percent_coverage": 100.0,
                            "median_depth": 5,
                            "min_non_zero_depth": 5,
                            "kmer_count": 108,
                            "klen": 21
                        },
                        "alternate": {
                            "percent_coverage": 14.29,
                            "median_depth": 0,
                            "min_non_zero_depth": 1,
                            "kmer_count": 393,
                            "klen": 22
                        }
                    },
                    "expected_depths": [
                        24
                    ],
                    "contamination_depths": [],
                    "filter": [],
                    "conf": 1390
                },
                "_cls": "Call.VariantCall"
            },

and for Nanopore

command used

$ mykrobe predict -e 0.08 --ploidy haploid -o /hps/nobackup/iqbal/mbhall/tech_wars/analysis/resistance_prediction/results/mykrobe/predict/nanopore/south_africa/R25048/R25048.mykrobe.json -i /hps/nobackup/iqbal/mbhall/tech_wars/data/QC/subsampled/south_africa/nanopore/R25048/R25048.subsampled.fastq.gz           --force -A --debug --format json --min_proportion_expected_depth 0.20 --sample R25048 --species tb           -t 4 -m 4096MB > /hps/nobackup/iqbal/mbhall/tech_wars/analysis/resistance_prediction/logs/rules/mykrobe/nanopore/south_africa/R25048.log 2>&1

            "katG_G1903GCT-C2154209AGC": {
                "variant": "ref-G1903GCT?var_name=C2154209AGC&num_alts=1&ref=NC_000962.3&enum=0&gene=katG&mut=G1903GCT",
                "genotype": [
                    0,
                    0
                ],
                "genotype_likelihoods": [
                    -157.54616831189273,
                    -10013.28801821664
                ],
                "info": {
                    "coverage": {
                        "reference": {
                            "percent_coverage": 100.0,
                            "median_depth": 96,
                            "min_non_zero_depth": 84,
                            "kmer_count": 1895,
                            "klen": 21
                        },
                        "alternate": {
                            "percent_coverage": 9.52,
                            "median_depth": 0,
                            "min_non_zero_depth": 87,
                            "kmer_count": 174,
                            "klen": 22
                        }
                    },
                    "expected_depths": [
                        100.0
                    ],
                    "contamination_depths": [],
                    "filter": [],
                    "conf": 9856
                },
                "_cls": "Call.VariantCall"
            },

I guess the two major questions here are

1. Why was this variant not added as evidence for isoniazid resistance in Illumina?
2. Why was this variant called homozygous ALT?