CRAIC: interactive interrogation of multiple sequence alignment uncertainty
- 1University of Liverpool
Abstract
Multiple sequence alignments (MSAs) are often treated as a solved problem. However, ambiguously or incorrectly aligned regions are the source of much error in phylogenetics and comparative genomics. CRAIC is a cross-platform desktop workbench that treats an alignment as a set of hypotheses to be stress-tested. CRAIC uses the posterior match probabilities of a three-state pair hidden Markov model (pair-HMM) to derive complementary views of alignment confidence. The five views are (i) a reliability overlay with live column and residue masking; (ii) a multi-aligner disagreement map, (iii) a local realignment sandbox, (iv) an interactive posterior explorer, and, where the true alignment is known, (v) a per-residue view of correctly predicted homologies. When present, MAFFT, MUSCLE, ProbCons, Clustal Omega, ClustalW and PRANK are integrated in the tool. In benchmarks the reliability score can locate misaligned columns, but while CRAIC can implement automatic filtering, it is primarily built for inspection and curation.
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BibTeX
@misc{mcinerney2026craic,
title = {{CRAIC: interactive interrogation of multiple sequence alignment uncertainty}},
author = {J. O. McInerney},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.756022},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.756022v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - CRAIC: interactive interrogation of multiple sequence alignment uncertainty
AU - J. O. McInerney
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.756022
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.756022v1
AB - Multiple sequence alignments (MSAs) are often treated as a solved problem. However, ambiguously or incorrectly aligned regions are the source of much error in phylogenetics and comparative genomics. CRAIC is a cross-platform desktop workbench that treats an alignment as a set of hypotheses to be stress-tested. CRAIC uses the posterior match probabilities of a three-state pair hidden Markov model (pair-HMM) to derive complementary views of alignment confidence. The five views are (i) a reliability overlay with live column and residue masking; (ii) a multi-aligner disagreement map, (iii) a local realignment sandbox, (iv) an interactive posterior explorer, and, where the true alignment is known, (v) a per-residue view of correctly predicted homologies. When present, MAFFT, MUSCLE, ProbCons, Clustal Omega, ClustalW and PRANK are integrated in the tool. In benchmarks the reliability score can locate misaligned columns, but while CRAIC can implement automatic filtering, it is primarily built for inspection and curation.
ER -