Take-home: substitution matrix quality matters. Instead of using ModelFinder, use IQ-Tree’s QMaker to build your own for your taxon of interest, trained on strictly filtered alignments. And use CLOAK before inferring trees. 10/10

For the sequence whose gene tree you are inferring, strict filters hurt, and our new gentle filter CLOAK performs best. Propagating uncertainty from our 16 variant alignments into a consensus among 16 variant trees was worse, showing the presence of systematic not just random alignment error. 9/10

Using a substitution model trained on strictly filtered alignment data leads to better inference on gene trees, bringing them closer to the known species tree according to Lin-Rajan-Moret distance (an improved extension of Robinson-Foulds distance). 8/10

Stricter filters have stronger effects in reducing exchangeabilities associated with less plausible amino acid substitutions, i.e. those that require more than one mutation, according to the genetic code. 7/10

Phylogenetics relies on substitution models (rates of evolution between amino acids or nucleotides), which are normally decomposed into a symmetric exchangeability matrix and equilibrium frequencies. Filtering reduces exchangeabilities between amino acids not linked by single mutations 6/10

In a trade-off between precision and recall, CLOAK is the best gentle filter, the “partial filtering” option within Divvier doi.org/10.1093/molb... is the best strict filter, and TAPER and the Divvier’s divvying option are in between. GUIDANCE2 and HmmCleaner perform less well. 5/10

Our new program CLOAK (CLeaning On Alignment C[K]onsensus) uses 16 variant alignments generated by Muscle5 (3 perturbations of HMM × 3 perturbations of guide tree), and retains only the pairs for which all 16 agree. You can call it within Muscle5 with the option “-cloak”. 4/10

Unfortunately, when building a gene tree, every bit of information can be important enough such that filtering alignments (at least with older tools) can make tree inference worse doi.org/10.1093/sysb... 3/10

Trigger warning: the attached images of real multiple sequence alignments may cause feelings of distress among biologists: 2/10

I have no idea about whether he is religious. I was responding to what you wrote about how the Nazis would have classified him, which has a clear factual answer.

I don't think what you say fits the facts: jewishjournal.com/news/united-...

@sashagusevposts.bsky.social, I would love to see a more detailed answer to this in particular. In your blog post, I couldn't find what I would call overwhelming, clearly laid out evidence re GxG and rares being minor contributions to broad-sense heritability in twin studies.