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Key outputs

Differentially modified output spreadsheet

Mako writes a TSV file of the following format:

differential/model_calls.tsv
transcript_id       transcript_position  rname                                                                                                               chr   chr_position  estimate              std_err              test_statistic        p_value               model_type     error  error_message        bh_corrected_p_value
ENST00000000233.10  145                  ENST00000000233.10|ENSG00000004059.11|OTTHUMG00000023246.7|OTTHUMT00000059567.3|ARF5-201|ARF5|1032|protein_coding|  chr7  127588556.0   0.28768207247673017   0.7936258469536126   0.3624908054356062    0.7169852932245568    binomial       False                       0.9640344056139295
ENST00000000233.10  178                  ENST00000000233.10|ENSG00000004059.11|OTTHUMG00000023246.7|OTTHUMT00000059567.3|ARF5-201|ARF5|1032|protein_coding|  chr7  127589106.0   0.1960495215844195    0.3689160678596121   0.531420392507882     0.5951274932453505    binomial       False                       0.9373782917763457
ENST00000000233.10  191                  ENST00000000233.10|ENSG00000004059.11|OTTHUMG00000023246.7|OTTHUMT00000059567.3|ARF5-201|ARF5|1032|protein_coding|  chr7  127589119.0   -0.7239188392266889   0.5913944974137653   -1.2240878844704635   0.220919075964312     binomial       False                       0.7249549006922915
ENST00000000233.10  195                  ENST00000000233.10|ENSG00000004059.11|OTTHUMG00000023246.7|OTTHUMT00000059567.3|ARF5-201|ARF5|1032|protein_coding|  chr7  127589123.0   0.49352123800261677   0.2511703485342725   1.9648865436649072    0.04942737051245885   binomial       False                       0.35089572319916346
ENST00000000233.10  229                  ENST00000000233.10|ENSG00000004059.11|OTTHUMG00000023246.7|OTTHUMT00000059567.3|ARF5-201|ARF5|1032|protein_coding|  chr7  127589157.0   -1.43281437674045     0.6961539005509063   -2.0581862367022326   0.039572259287345535  binomial       False                       0.307126201446428
...

Column
Description
transcript_id Transcript ID the site belongs to, extracted from rname
transcript_position Transcript position of the site
rname Full reference transcript annotation string
chr Chromosome of the site
chr_position Genomic position of the site
estimate Effect size estimate from the differential model
std_err Standard error of the estimate
test_statistic Test statistic
p_value Raw p-value for the test of differential modification at this site
model_type Statistical model used to analyse the site (e.g. binomial, homo_norm, hetero_norm, beta_binomial)
error Whether the model fit failed for this site (True/False)
error_message Error message if error is True, otherwise typically blank/NA
bh_corrected_p_value Benjamini–Hochberg corrected p-value

Makoview launch script

Makoview is a visualisation tool to view the output of Mako. It is automatically installed and can be launched using the script makoview/launch_makoview.sh.

All outputs

Directory tree of Mako outputs
outdir/
├── basecall
│   ├── <sample, e.g. H146>
│   │   ├── basecalled_sorted.bam
│   │   ├── basecalled_sorted.bam.bai
│   │   ├── H146_fastqc.html
│   │   ├── H146_fastqc.zip
│   │   ├── H146.flagstat.txt
│   │   └── 📁 nanoplot
│   ├── 📁 nanocomp
├── db
│   ├── coverage.duckdb
│   └── reads.duckdb
├── differential
│   ├── model_calls.tsv
│   ├── segments/*.parquet
│   ├── segments.csv
│   └── sites.duckdb
├── makoview
│   ├── launch_makoview.sh
│   └── 📁 makoview_venv
└── modcall
    └── <sample, e.g. H146>
        ├── modifications_H146.tsv.gz
        ├── pileup_H146.bed.gz
        └── pileup_H146.bed.gz.tbi

basecall/ directory

Per-sample basecalling and alignment QC.

File Description
basecalled_sorted.bam(.bai) Coordinate-sorted, indexed alignments from dorado
{sample}_fastqc.html/.zip FastQC report on basecalled reads
{sample}.flagstat.txt samtools flagstat summary
nanoplot/ Per-sample NanoPlot QC report
nanocomp/ Cross-sample comparison (NanoComp) — read length, N50, throughput, identity, quality plots

modcall/ directory

Per-sample RNA modification analyses (modkit).

File Description
pileup_{sample}.bed.gz(.tbi) bedMethyl pileup of per-site modification stats
modifications_{sample}.tsv.gz Read-level modification analyses

db/ directory

Aggregated databases used internally by the differential step.

File Description
reads.duckdb Read-level modification data across samples
coverage.duckdb Per-site coverage across samples

differential/ directory

Differential modification analysis outputs.

File Description
model_calls.tsv Final differential analysis results
sites.duckdb Selected/filtered sites used for testing
segments.csv Genomic segments used to parallelise analysis
segments/*.parquet Per-segment intermediate results

makoview/

Interactive results viewer.

File Description
launch_makoview.sh Script to launch the viewer
makoview_venv/ Bundled Python virtual environment for the viewer