Retinal imaging of the mouse eye with its small pupil has been a challenge because of the difficult alignment of light delivered to the eye.
In fact, difficult alignment between segmented mirrors requires a complex support structure, which mostly erases its lightweight advantage relative to MiXO.
For the more difficult alignment tests, e.g. with norMD<0.2, the mean CS scores were less than 0.5 for all the aligners included in this study.
The difficult alignment test sets are taken from Table 1 of their publication (ADP-ribosylating toxins (SCOP folds d.166.1.1) and Poly-ADP-ribose polymerase (d.166.1.2)[10].
The shortcomings of such devices include the following: incompatibility with microarray scanners [19], small heating zones [19], [20], limited temperature control [20], complex fabrication [19], and difficult alignment of DNA microarrays [19], [20].
To simulate more difficult alignment cases where the candidate sequence is distant to the closest match in the reference MSA, reference sequence selection may be constrained using a maximum identity parameter.
The most similar sequences will be the easiest to align most accurately and this delays the more difficult alignments until last.
To further flag difficult alignments in homo- and dipolymer runs as well as short simple sequence repeats, sequence complexity was defined by different triplets around the focal position.
Finally, to evaluate whether the 'sieving' method was able to identify residues of functional relevance for "difficult" alignments, it was applied to two FAD binding domains, d1gt8a4 and d1mo9a1 (Case (D), SCOP folds c.4.1.1.1 and c.3.1.5 respectively).
This is a difficult problem for multiple alignment programs such as CLUSTALW or T-COFFEE, which work well for closely related proteins but which are not designed to compare highly divergent proteins with differing architectures.
However, achieving such an alignment is a difficult challenge; especially when taking into account that such transformations require solid governance, trust and high initial investments — prerequisites that are rare in many public-private partnerships.
