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A comparison of the manual exclusion of vessel structures and the CCA revealed an average reduction of 13% for the PBV and 8% for PBF.
We found that MIDAS had generally moderate to good agreement with the manual reference method for the presence of lobar microbleeds (Kappa = 0.43, improved to 0.65 after manual exclusion of obvious artefacts).
The normalization on the TIC with manual exclusion of the aberrant peak (Fig. 7D) shows the smoothest distribution.
Although normalization to the noise level or the median could be used to generate normalized images without artifacts, TIC normalization with the manual exclusion of the signals that caused the artifacts produced the best results.
Further, we investigated other novel normalization approaches which, to our knowledge, have not been applied to imaging data, such as median normalization or TIC normalization with manual exclusion of mass ranges.
Phylogenetic trees were inferred from the eleven alignments (without further processing such as a manual re-alignment or manual exclusion of sites) under the maximum likelihood (ML) criterion with RAxML version 7.04.
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Paternity was assigned by manual exclusion.
Once the inapplicability of TIC-based normalization is established, it is usually simple to spot the problematic peaks for a manual exclusion.
In order to increase the quality of the alignment, both manual curation and exclusion of gaps columns were performed prior to phylogenetic reconstruction.
In addition, we also used manual inclusion and exclusion of features.
Details of the grading process and segmentation correction procedures were updated in the methods section under the subheading "Error determination, manual correction, and exclusion of scans".
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