CHOICE and CLIPS are two unsupervised learning algorithms developed to implement BRIDGEcereal webapp, which is constructed to survey and graph large indel based haplotype graph from publicly accessible pan-genomes for a gene of interest.
A large indel, if presents, is indicated by two flanking High-scoring Segment Pairs (HSPs) for a pair of segments identified by Blastn. A Pan-genome with multiple assemblies enables the possibility to identify large indels from a gene of interest through the desired All-vs-All comparison. However, two main challenges are:
- Identification of the segment containing the ortholog from each assembly.
- Visualization of identified indels from a large number of assemblies.
CHOICE and CLIPS are developed to tackle these two challenges, respectively. TraesCS4A02G058900 was used as the demonstration how CHOICE and CLIPS work in tandeam to graph indel based haplotypes.
(R library dendextend and data.table are required to go through the demonstration)
CHOICE, Clustering HSPs for Ortholog Identification via Coordinates and Equivalence, identifies and extracts the segment harboring the ortholog from each assembly.
CDS of TraesCS4A02G058900 is searched against chr4A of each assembly (11 in total) via Blastn. The Blastn output (-outfmt 6) is reorganized as TraesCS4A02G058900_syn.txt, which is the input for CHOICE. CHOICE which will determine the region of each assembly contain the ortholog. For example, the coordinates for variety spelta are from 52,231,267 to 52,245,777, while are from 52,859,043 to 52,873,560 for variety lancer. The coordinates will be then used to exact the corresponding segment out from each assembly. Two output files (CHOICE_summary.txt and Filtered_By_CHOICE.txt) will be also saved.
CLIPS (Clustering via Large-Indel Permuted Slopes) groups segments sharing the same set of indels into haplotypes. For a pair of segments, the slope estimate is one when large indels are absent, but deviates from one when large indels are present.
These extraced segments are then blasted against each other via Blastn (-outfmt 6). The output file TraesCS4A02G058900_seg-Self_out_m6.txt is then fed into CLIPS. The clustering tree suggests two main haplotypes for this gene: one is only detected in by Chinese Spring, while another haplotype is shared by all other varieties. One output file "slope_matrix_output_from_CLIPS.txt" will be also saved.
Visualize the alignments and slope estimates by adjusting HSP parameters in the first coding block.
Zhang B, Huang H, Tibbs-Cortes LE, Vanous A, Zhang Z, Sanguinet K, Garland-Campbell KA, Yu J, Li X. Streamline unsupervised machine learning to survey and graph indel-based haplotypes from pan-genomes. bioRxiv. 2023. doi: 10.1101/2023.02.11.527743