Dragen alignment failing/terminating
0
0
Entering edit mode
5.2 years ago
Floydian_slip ▴ 170

Hi, I am running Dragen on my sample for alignment and it terminates/exits early without any error. I am new to the Dragen alignment world. I was wondering if there is anything in the .out file (copied below) which could hint if its a Dragen issue or a hardware issue? Can anybody advise me on what could be going wrong? I am also copying the small .err file at the end of the message. Thanks!

==================================================================
Writing reference to card memory
==================================================================
Sending 32212254720 bytes to card address 0x0
Sending 1524944896 bytes to card address 0x780000000
Sending 47654656 bytes to card address 0x7dae4d000

==================================================================
DNA Mapper/Aligner Configuration
==================================================================

    config-file:                       /nfs/seqscratch_ssd/ALIGNMENT/BUILD37/DRAGEN/GENOME/sqcudn748499.199027/scripts/sqcudn748499.199027.DragenAlignment.203917..1.conf
    fastq-file1:                       /nfs/tx/in/4928/sqcudn748499/FASTQ/895401-UDN748499-P_L001_R1_1.fastq.gz
    fastq-file2:                       /nfs/tx/in/4928/sqcudn748499/FASTQ/895401-UDN748499-P_L001_R2_1.fastq.gz
    ref-dir:                           /staging/REF/b37_decoy/
    ref-config:                        not alt-aware capable
    alt-aware:                         false
    intermediate-results-dir:          /staging/tmp
    output-directory:                  /nfs/seqscratch_ssd/ALIGNMENT/BUILD37/DRAGEN/GENOME/sqcudn748499.199027/
    output-file-prefix:                sqcudn748499.199027..1

output-format:                     BAM
enable-map-align:                  true
auto-pe-stats-detection:           enabled
pe-stats-continuous-update:        disabled
pe-stats-update-log-only:          disabled
enable-map-align-output:           true
enable-sort:                       true
enable-duplicate-marking:          true
remove-duplicates:                 false
methylation-protocol:              none

==================================================================
Processing reads
==================================================================
LICENSE_MSG|  Requested streams: DNA mapper(x1) unzip(x2) zip(x1)
LICENSE_MSG|   Board AC05142591657, CHIPID=0050F10A097EB01C
LICENSE_MSG|  Requested streams: DNA mapper(x1) unzip(x2) zip(x1)
LICENSE_MSG|   Board AC05142591657, CHIPID=0050F10A097EB01C
LICENSE_MSG|  Allocation:
LICENSE_MSG|   #0: board 0 stream 0, DNA mapper|DBAM loopback|Simple loopback|memory -> DNA mapper
LICENSE_MSG|   #1: board 0 stream 1, DBAM loopback|Simple loopback|unzip|zip -> unzip
LICENSE_MSG|   #2: board 0 stream 2, DBAM loopback|Simple loopback|unzip|zip -> unzip
LICENSE_MSG|   #3: board 0 stream 3, DBAM loopback|Simple loopback|zip -> zip
Opening FASTQ file 895401-UDN748499-P_L001_R1_1.fastq.gz
Opening FASTQ file 895401-UDN748499-P_L001_R2_1.fastq.gz
Dividing sort intermediate data into 1146 partitions for mapped, and an equal number for unmapped, records.
  predicted_output_size :  1006GB
  max_bin_size          :  900MB
  total_system_memory   :  125GB
  total_bin_memory      :  20GB
  sort_buffer_size      :  1024kB
  predicted_num_bins    :  1146
  max_num_bins          :  8192
  num_bins              :  1146
  sort_threads          :  4
  dedup_threads         :  4
  dbam2bam_threads      :  32

Initial paired-end statistics detected for read group 0, based on 91244 high quality pairs for FR orientation
        Quartiles (25 50 75) = 491 602 725
        Mean = 605.864
        Standard deviation = 188.04
        Rescue radius = 446.925
        Effective rescue sigmas = 2.37676
        WARNING: Default rescue sigmas value of 2.5 was overridden by host software!
        The user may wish to set a rescue sigmas value explicitly with --Aligner.rescue-sigmas
        Boundaries for mean and standard deviation: low = 23, high = 1193
        Boundaries for proper pairs: low = 1, high = 1427
        NOTE: DRAGEN's insert estimates include corrections for clipping (so they are not identical to TLEN)
read A00307:69:HJVYTDSXX:1:2550:2844:4163 id = 0x6A9C9E27
read A00307:69:HJVYTDSXX:1:2550:2844:4163 id = 0x6A9C9E27
Closing FASTQ file 895401-UDN748499-P_L001_R1_1.fastq.gz
Closing FASTQ file 895401-UDN748499-P_L001_R2_1.fastq.gz

Finished - processed 2292024624 reads (1146012312 pairs)
LICENSE_MSG|  Requested streams: DNA mapper(x1) zip(x3)
LICENSE_MSG|   Board AC05142591657, CHIPID=0050F10A097EB01C
LICENSE_MSG|  Requested streams: DNA mapper(x1) zip(x3)
LICENSE_MSG|   Board AC05142591657, CHIPID=0050F10A097EB01C
LICENSE_MSG|  Allocation:
LICENSE_MSG|   #0: board 0 stream 0, DNA mapper|DBAM loopback|Simple loopback|memory -> DNA mapper
LICENSE_MSG|   #1: board 0 stream 1, DBAM loopback|Simple loopback|unzip|zip -> zip
LICENSE_MSG|   #2: board 0 stream 2, DBAM loopback|Simple loopback|unzip|zip -> zip
LICENSE_MSG|   #3: board 0 stream 3, DBAM loopback|Simple loopback|zip -> zip

==================================================================
Sorting
==================================================================
Paired-end statistics were based on initial reads for read group 0, based on 91244 high quality pairs for FR orientation
Paired-end statistics were based on initial reads for read group 0, based on 91244 high quality pairs for FR orientation
        Quartiles (25 50 75) = 491 602 725
        Mean = 605.864
        Standard deviation = 188.04
        Rescue radius = 446.925
        Effective rescue sigmas = 2.37676
        WARNING: Default rescue sigmas value of 2.5 was overridden by host software!
        The user may wish to set a rescue sigmas value explicitly with --Aligner.rescue-sigmas
        Boundaries for mean and standard deviation: low = 23, high = 1193
        Boundaries for proper pairs: low = 1, high = 1427
        NOTE: DRAGEN's insert estimates include corrections for clipping (so they are not identical to TLEN)
LICENSE_MSG| ***********************************************************
LICENSE_MSG| Licenses status:
LICENSE_MSG|   Genome          : used 600669.5/725000 Gbases since 2019-Sep-01 (600669488161648 bases, 82.9%)
LICENSE_MSG|

==================================================================
DRAGEN METRICS
==================================================================

MAPPING/ALIGNING SUMMARY               Total input reads                                       2292024624
MAPPING/ALIGNING SUMMARY               Number of duplicate reads (marked)                      34763650       1.52
MAPPING/ALIGNING SUMMARY               Number of unique reads                                  2257260974     98.48
MAPPING/ALIGNING SUMMARY               Reads with mate sequenced                               2292024624     100.00
MAPPING/ALIGNING SUMMARY               Reads without mate sequenced                            0              0.00
MAPPING/ALIGNING SUMMARY               QC-failed reads                                         0              0.00
MAPPING/ALIGNING SUMMARY               Mapped reads                                            2263601179     98.76
MAPPING/ALIGNING SUMMARY               Number of unique & mapped reads (excl. dups)            2228837529     97.24
MAPPING/ALIGNING SUMMARY               Unmapped reads                                          28423445       1.24
MAPPING/ALIGNING SUMMARY               Singleton reads (itself mapped; mate unmapped)          7736139        0.34
MAPPING/ALIGNING SUMMARY               Paired reads (itself & mate mapped)                     2255865040     98.42
MAPPING/ALIGNING SUMMARY               Properly paired reads                                   2217096062     96.73
MAPPING/ALIGNING SUMMARY               Not properly paired reads (discordant)                  38768978       1.69
MAPPING/ALIGNING SUMMARY               Reads with MAPQ [40:inf)                                2095632883     91.43
MAPPING/ALIGNING SUMMARY               Reads with MAPQ [30:40)                                 9595781        0.42
MAPPING/ALIGNING SUMMARY               Reads with MAPQ [20:30)                                 24156035       1.05
MAPPING/ALIGNING SUMMARY               Reads with MAPQ [10:20)                                 32443054       1.42
MAPPING/ALIGNING SUMMARY               Reads with MAPQ [ 0:10)                                 101773426      4.44
MAPPING/ALIGNING SUMMARY               Total alignments                                        2267967248
MAPPING/ALIGNING SUMMARY               Secondary alignments                                    0
MAPPING/ALIGNING SUMMARY               Supplementary (chimeric) alignments                     4366069
MAPPING/ALIGNING SUMMARY               Estimated read length                                   148.92
MAPPING/ALIGNING SUMMARY               Bases in reference genome                               3137454505
MAPPING/ALIGNING SUMMARY               Bases in target bed [% of genome]                       NA
MAPPING/ALIGNING SUMMARY               Average sequenced coverage over genome                  108.79
MAPPING/ALIGNING SUMMARY               Average alignment coverage over genome                  NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [40x:inf)                   NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [30x:40x)                   NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [20x:30x)                   NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [10x:20x)                   NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [ 5x:10x)                   NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [ 2x: 5x)                   NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [ 1x: 2x)                   NA
MAPPING/ALIGNING SUMMARY               PCT of genome with coverage [ 0x: 1x)                   NA
MAPPING/ALIGNING SUMMARY               DRAGEN mapping rate [mil. reads/second]                 0.83

MAPPING/ALIGNING PER RG       .1       Total reads in RG                                       2292024624     100.00
MAPPING/ALIGNING PER RG       .1       Number of duplicate reads (marked)                      34763650       1.52
MAPPING/ALIGNING PER RG       .1       Number of unique reads                                  2257260974     98.48
MAPPING/ALIGNING PER RG       .1       Reads with mate sequenced                               2292024624     100.00
MAPPING/ALIGNING PER RG       .1       Reads without mate sequenced                            0              0.00
MAPPING/ALIGNING PER RG       .1       QC-failed reads                                         0              0.00
MAPPING/ALIGNING PER RG       .1       Mapped reads                                            2263601179     98.76
MAPPING/ALIGNING PER RG       .1       Number of unique & mapped reads (excl. dups)            2228837529     97.24
MAPPING/ALIGNING PER RG       .1       Unmapped reads                                          28423445       1.24
MAPPING/ALIGNING PER RG       .1       Singleton reads (itself mapped; mate unmapped)          7736139        0.34
MAPPING/ALIGNING PER RG       .1       Paired reads (itself & mate mapped)                     2255865040     98.42
MAPPING/ALIGNING PER RG       .1       Properly paired reads                                   2217096062     96.73
MAPPING/ALIGNING PER RG       .1       Not properly paired reads (discordant)                  38768978       1.69
MAPPING/ALIGNING PER RG       .1       Reads with MAPQ [40:inf)                                2095632883     91.43
MAPPING/ALIGNING PER RG       .1       Reads with MAPQ [30:40)                                 9595781        0.42
MAPPING/ALIGNING PER RG       .1       Reads with MAPQ [20:30)                                 24156035       1.05
MAPPING/ALIGNING PER RG       .1       Reads with MAPQ [10:20)                                 32443054       1.42
MAPPING/ALIGNING PER RG       .1       Reads with MAPQ [ 0:10)                                 101773426      4.44
MAPPING/ALIGNING PER RG       .1       Total alignments                                        2267967248
MAPPING/ALIGNING PER RG       .1       Secondary alignments                                    0
MAPPING/ALIGNING PER RG       .1       Supplementary (chimeric) alignments                     4366069
MAPPING/ALIGNING PER RG       .1       Estimated read length                                   148.92
MAPPING/ALIGNING PER RG       .1       Average sequenced coverage over genome                  108.79
MAPPING/ALIGNING PER RG       .1       Insert length: mean                                     605.86
MAPPING/ALIGNING PER RG       .1       Insert length: standard deviation                       188.04

RUN TIME                               Time loading reference                                  00:01:00.333   60.33
RUN TIME                               Time aligning reads                                     00:45:37.964   2737.96
RUN TIME                               Time sorting and marking duplicates                     00:13:48.195   828.20
RUN TIME                               Time saving map/align output                            00:13:52.870   832.87
RUN TIME                               Total runtime                                           01:02:20.192   3740.19
==================================================================

The .err file content:

Spilling sort intermediate results to disk
Partitioning complete.  Lowest evicted: 36
dragen alignment • 2.2k views
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1
Entering edit mode

This might be something to resolve with the Edico/Illumina engineers directly.

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0
Entering edit mode

Strange, for me it looks like the alignment ran through successfully, e.g.

MAPPING/ALIGNING SUMMARY Number of unique & mapped reads (excl. dups) 2228837529 97.24

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0
Entering edit mode

This can depend on the reference genome as well as the sample that is processed. We used the DRAGEN for wheat genomics (reference sizes between 12 and 17Gbp) and that didn't work 100% in the beginning. We had a massive number of exome capture samples and some of those would cause problems. In the case of the reference, the size was definitely an issue, but also the high repetitive fraction potentially caused trouble. As for the samples, I never found out why certain samples had problems (sometimes it also seemed that the DRAGEN was "exhausted" after processing 100s of samples.)

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