Classification of ecDNAs

[silkrp]

Hi, following up on our discussion in #59, I’ve been reviewing the CoRAL output for one of our samples (E25) and was wondering which files and fields should be used to identify the ecDNA predicted by CoRAL.

In the *.bed file output by CoRAL, it appears to suggests that CoRAL detected two ecDNAs (cycle_id 1 and cycle_id 2), both marked as iscyclic = True. This is assuming that when iscyclic is TRUE it refers to an ecDNA amplicon, and that each cycle_id refers to a different ecDNA amplicon. The file looks as follows:

#chr    start   end     orientation     cycle_id        iscyclic        weight
chr12   68289411        68296626        +       1       True    280.03069256391854
chr12   68376688        68418711        -       1       True    280.03069256391854
chr12   68683243        69112846        -       1       True    280.03069256391854
chr4    53542873        53546479        +       2       True    35.20001540165041
chr12   69116164        69210212        +       2       True    35.20001540165041
chr12   57732353        57759576        +       2       True    35.20001540165041
chr12   67440960        67653722        +       2       True    35.20001540165041
chr12   68360060        68376613        +       2       True    35.20001540165041
chr12   69112911        69210212        +       2       True    35.20001540165041
chr12   57732353        58010216        +       2       True    35.20001540165041
chr4    55226054        55237799        +       2       True    35.20001540165041

However, the corresponding amplicon_summary.txt for this sample only reports details for a single amplicon (AmpliconID = 1). Which looks to be cycle_id 2 in the previous bed file. This file looks as follows:

CoRAL v2.2.0
1/1 amplicons solved.
Runtime Limit: 21600 s
Profiling Enabled: False
-----------------------------------------------
AmpliconID = 1
#Intervals = 5
AmpliconIntervals:
        Amplicon0>chr4:53,438,912-54,728,886
        Amplicon0>chr4:54,923,878-55,499,030
        Amplicon0>chr12:57,630,264-58,121,487
        Amplicon0>chr12:64,120,264-64,851,857
        Amplicon0>chr12:67,340,269-69,310,269
Total Amplicon Size: 5,057,947
# Chromosomes: 2
# Sequence Edges: 57
# Concordant Edges: 52
# Discordant Edges: 26
# Non-Source Edges: 135
# Source Edges: 0
Cycle Decomposition Status: SUCCESS
        ModelMetadata: GREEDY, k=9, alpha=0.01, total_weights=195158103.68227065, resolution=0.1, num_path_constraints=21
        Heaviest graph walk solved was a cycle.
        Cycle=1;Copy_count=280.03069256391854;Segments=37+,41-,53-,52-,51-,50-,49-,48-,47-,46-,45-,44-,43-

Does the *.bed file indicate two distinct ecDNAs, or is one of the cycles (cycle_id 1) later filtered out as being an ecDNA at a later stage?

Any clarification on how to interpret multiple cycle_id's in the BED file versus the summary output would be much appreciated, and ideally which CoRAL files contain the final set of ecDNA predictions?