@HD VN:1.4 SO:coordinate @RG ID:1#8 PL:ILLUMINA PU:150908_HS38_17534_B_C75B6ANXX_6#8 LB:14290740 DS:EGAS00001000858: AML emerges as a consequence of accumulating independent genetic aberrations that direct regulation and/or dysfunction of genes resulting in aberrant activation of signalling pathways, resistance to apoptosis and uncontrolled proliferation. Given the significant heterogeneity of AML genomes, AML patients demonstrate a highly variable response rate and poor median survival in response to current chemotherapy regimens. For the past 4 years we have conducted gene expression profiling on purified bone marrow populations equating to normal haematopoietic stem and progenitor cells from healthy subjects and patients with de novo AML in order to identify AML signatures of aberrantly expressed genes in cancer versus normal. We are now applying a series of bioinformatic methodologies combined with clinical and conventional diagnostic data to establish novel genomics strategies for improved prognostication of AML. Additionally, we use our AML signatures to unravel oncogenic signalling pathway activities in AML patients and test inhibitory drugs for these pathways inn preclinical therapeutic programmes. We consider that superimposing GEP and clinical data for our AML patient cohort with additional data on their mutational status will significantly improve the prognostic power of the study as well as unravel yet unknown mutations associated with aberrant signalling activities of oncogenic pathways. DT:2015-09-08T00:00:00+0100 SM:EGAN00001259057 PG:BamIndexDecoder CN:SC @PG ID:SCS PN:HiSeq Control Software DS:Controlling software on instrument VN:2.2.68 @PG ID:basecalling PN:RTA PP:SCS DS:Basecalling Package VN:1.18.66.3 @PG ID:Illumina2bam PN:Illumina2bam PP:basecalling DS:Convert Illumina BCL to BAM or SAM file VN:V1.17 CL:uk.ac.sanger.npg.illumina.Illumina2bam INTENSITY_DIR=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities BASECALLS_DIR=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BaseCalls LANE=6 OUTPUT=/dev/stdout SAMPLE_ALIAS=EGAN00001259050,EGAN00001259051,EGAN00001259052,EGAN00001259053,EGAN00001259054,EGAN00001259055,EGAN00001259056,EGAN00001259057,EGAN00001259058,EGAN00001259059,EGAN00001259060,EGAN00001259061,EGAN00001259062,EGAN00001259063,EGAN00001259064,EGAN00001259065,EGAN00001259066,EGAN00001259067,EGAN00001259068,EGAN00001259069,EGAN00001259070,EGAN00001259071,EGAN00001259072,EGAN00001259073,EGAN00001259074,EGAN00001259075,EGAN00001259076,EGAN00001259077,EGAN00001259078,EGAN00001259079,EGAN00001259080,EGAN00001259081,EGAN00001259082,EGAN00001259083,EGAN00001259084,EGAN00001259085 STUDY_NAME=EGAS00001000858: AML emerges as a consequence of accumulating independent genetic aberrations that direct regulation and/or dysfunction of genes resulting in aberrant activation of signalling pathways, resistance to apoptosis and uncontrolled proliferation. Given the significant heterogeneity of AML genomes, AML patients demonstrate a highly variable response rate and poor median survival in response to current chemotherapy regimens. For the past 4 years we have conducted gene expression profiling on purified bone marrow populations equating to normal haematopoietic stem and progenitor cells from healthy subjects and patients with de novo AML in order to identify AML signatures of aberrantly expressed genes in cancer versus normal. We are now applying a series of bioinformatic methodologies combined with clinical and conventional diagnostic data to establish novel genomics strategies for improved prognostication of AML. Additionally, we use our AML signatures to unravel oncogenic signalling pathway activities in AML patients and test inhibitory drugs for these pathways inn preclinical therapeutic programmes. We consider that superimposing GEP and clinical data for our AML patient cohort with additional data on their mutational status will significantly improve the prognostic power of the study as well as unravel yet unknown mutations associated with aberrant signalling activities of oncogenic pathways. PLATFORM_UNIT=150908_HS38_17534_B_C75B6ANXX_6 COMPRESSION_LEVEL=0 GENERATE_SECONDARY_BASE_CALLS=false PF_FILTER=true READ_GROUP_ID=1 LIBRARY_NAME=unknown SEQUENCING_CENTER=SC PLATFORM=ILLUMINA BARCODE_SEQUENCE_TAG_NAME=BC BARCODE_QUALITY_TAG_NAME=QT ADD_CLUSTER_INDEX_TAG=false VERBOSITY=INFO QUIET=false VALIDATION_STRINGENCY=STRICT MAX_RECORDS_IN_RAM=500000 CREATE_INDEX=false CREATE_MD5_FILE=false @PG ID:bamadapterfind PN:bamadapterfind PP:Illumina2bam VN:2.0.16 CL:bamadapterfind level=0 @PG ID:BamIndexDecoder PN:BamIndexDecoder PP:bamadapterfind DS:A command-line tool to decode multiplexed bam file VN:V1.17 CL:uk.ac.sanger.npg.picard.BamIndexDecoder INPUT=/dev/stdin OUTPUT=/dev/stdout BARCODE_FILE=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/metadata_cache_17534/lane_6.taglist METRICS_FILE=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/17534_6.bam.tag_decode.metrics VALIDATION_STRINGENCY=SILENT CREATE_MD5_FILE=false BARCODE_TAG_NAME=BC BARCODE_QUALITY_TAG_NAME=QT MAX_MISMATCHES=1 MIN_MISMATCH_DELTA=1 MAX_NO_CALLS=2 CONVERT_LOW_QUALITY_TO_NO_CALL=false MAX_LOW_QUALITY_TO_CONVERT=15 VERBOSITY=INFO QUIET=false COMPRESSION_LEVEL=5 MAX_RECORDS_IN_RAM=500000 CREATE_INDEX=false @PG ID:spf PN:spatial_filter PP:BamIndexDecoder DS:A program to apply a spatial filter VN:v10.23 CL:/software/solexa/pkg/pb_calibration/v10.23/bin/spatial_filter -c -F pb_align_17534_6.bam.filter -t /nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/no_cal/archive/qc/tileviz/17534_6 --region_size 200 --region_mismatch_threshold 0.0160 --region_insertion_threshold 0.0160 --region_deletion_threshold 0.0160 pb_align_17534_6.bam ; /software/solexa/pkg/pb_calibration/v10.23/bin/spatial_filter -a -f -u -F pb_align_17534_6.bam.filter - @PG ID:bwa PN:bwa PP:spf VN:0.5.10-tpx @PG ID:BamMerger PN:BamMerger PP:bwa DS:A command-line tool to merge BAM/SAM alignment info in the first input file with the data in an unmapped BAM file, producing a third BAM file that has alignment data and all the additional data from the unmapped BAM VN:V1.17 CL:uk.ac.sanger.npg.picard.BamMerger ALIGNED_BAM=pb_align_17534_6.bam INPUT=/dev/stdin OUTPUT=17534_6.bam KEEP_EXTRA_UNMAPPED_READS=true REPLACE_ALIGNED_BASE_QUALITY=true VALIDATION_STRINGENCY=SILENT CREATE_MD5_FILE=true ALIGNMENT_PROGRAM_ID=bwa KEEP_ALL_PG=false VERBOSITY=INFO QUIET=false COMPRESSION_LEVEL=5 MAX_RECORDS_IN_RAM=500000 CREATE_INDEX=false @PG ID:SplitBamByReadGroup PN:SplitBamByReadGroup PP:BamMerger DS:Split a BAM file into multiple BAM files based on ReadGroup. Headers are a copy of the original file, removing @RGs where IDs match with the other ReadGroup IDs VN:V1.17 CL:uk.ac.sanger.npg.picard.SplitBamByReadGroup INPUT=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/no_cal/17534_6.bam OUTPUT_PREFIX=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/no_cal/lane6/17534_6 OUTPUT_COMMON_RG_HEAD_TO_TRIM=1 VALIDATION_STRINGENCY=SILENT CREATE_MD5_FILE=true VERBOSITY=INFO QUIET=false COMPRESSION_LEVEL=5 MAX_RECORDS_IN_RAM=500000 CREATE_INDEX=false @PG ID:bamcollate2 PN:bamcollate2 PP:SplitBamByReadGroup VN:2.0.16 CL:/software/solexa/pkg/biobambam/2.0.16/bin/bamcollate2 collate=1 level=0 @PG ID:bamreset PN:bamreset PP:bamcollate2 VN:2.0.16 CL:/software/solexa/pkg/biobambam/2.0.16/bin/bamreset resetaux=0 level=0 verbose=0 @PG ID:bamadapterclip PN:bamadapterclip PP:bamreset VN:2.0.16 CL:/software/solexa/pkg/biobambam/2.0.16/bin/bamadapterclip verbose=0 level=0 @PG ID:bwa' PN:bwa PP:bamadapterclip VN:0.7.12-r1039 CL:/software/solexa/pkg/bwa/bwa-0.7.12/bwa mem -t 16 -p -T 0 /lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/bwa0_6/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa /tmp/k7724uspK1/alntgt_bamtofastq_out @PG ID:scramble PN:scramble PP:bwa' VN:1.14.0 CL:/software/solexa/pkg/scramble/1.14.0/bin/scramble -I sam -O bam @PG ID:bam12split PN:bam12split PP:scramble VN:2.0.16 CL:/software/solexa/pkg/biobambam/2.0.16/bin/bam12split verbose=0 level=0 @PG ID:bamsort PN:bamsort PP:bam12split VN:2.0.16 CL:/software/solexa/pkg/biobambam/2.0.16/bin/bamsort SO=queryname level=0 @PG ID:AlignmentFilter PN:AlignmentFilter PP:bamsort DS:Give a list of SAM/BAM files with the same set of records and in the same order but aligned with different references, split reads into different files according to alignments. You have option to put unaligned reads into one of output files or a separate file VN:V1.17 CL:uk.ac.sanger.npg.picard.AlignmentFilter INPUT_ALIGNMENT=[./initial_phix_aln_17534_6#8.bam, /tmp/LjEXJyhcUs/postalntgt_bam12auxmerge_out] OUTPUT_ALIGNMENT=[/tmp/wadoXHt2K3/alignment_filter:__PHIX_OUTBAM___out, /dev/stdout] METRICS_FILE=17534_6#8.bam_alignment_filter_metrics.json VERBOSITY=INFO QUIET=false VALIDATION_STRINGENCY=SILENT COMPRESSION_LEVEL=5 MAX_RECORDS_IN_RAM=500000 CREATE_INDEX=false CREATE_MD5_FILE=false @PG ID:bamsort' PN:bamsort CL:/software/solexa/pkg/biobambam/2.0.16/bin/bamsort SO=coordinate level=0 verbose=0 fixmate=1 adddupmarksupport=1 tmpfile=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/no_cal/archive/lane6/bsfopt_17534_6#8.tmp PP:AlignmentFilter VN:2.0.16 @PG ID:bamstreamingmarkduplicates PN:bamstreamingmarkduplicates CL:/software/solexa/pkg/biobambam/2.0.16/bin/bamstreamingmarkduplicates level=0 verbose=0 tmpfile=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/no_cal/archive/lane6/bmdfopt_17534_6#8.tmp M=/nfs/sf29/ILorHSany_sf29/analysis/150908_HS38_17534_B_C75B6ANXX/Data/Intensities/BAM_basecalls_20150912-062433/no_cal/archive/lane6/17534_6#8.markdups_metrics.txt PP:bamsort' VN:2.0.16 @PG ID:scramble.1 PN:scramble PP:bamstreamingmarkduplicates VN:1.14.0 CL:/software/solexa/pkg/scramble/1.14.0/bin/scramble -I bam -O cram -r /lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa @SQ SN:1 LN:249250621 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:1b22b98cdeb4a9304cb5d48026a85128 SP:Homo sapiens @SQ SN:2 LN:243199373 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:a0d9851da00400dec1098a9255ac712e SP:Homo sapiens @SQ SN:3 LN:198022430 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:fdfd811849cc2fadebc929bb925902e5 SP:Homo sapiens @SQ SN:4 LN:191154276 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:23dccd106897542ad87d2765d28a19a1 SP:Homo sapiens @SQ SN:5 LN:180915260 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:0740173db9ffd264d728f32784845cd7 SP:Homo sapiens @SQ SN:6 LN:171115067 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:1d3a93a248d92a729ee764823acbbc6b SP:Homo sapiens @SQ SN:7 LN:159138663 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:618366e953d6aaad97dbe4777c29375e SP:Homo sapiens @SQ SN:8 LN:146364022 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:96f514a9929e410c6651697bded59aec SP:Homo sapiens @SQ SN:9 LN:141213431 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:3e273117f15e0a400f01055d9f393768 SP:Homo sapiens @SQ SN:10 LN:135534747 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:988c28e000e84c26d552359af1ea2e1d SP:Homo sapiens @SQ SN:11 LN:135006516 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:98c59049a2df285c76ffb1c6db8f8b96 SP:Homo sapiens @SQ SN:12 LN:133851895 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:51851ac0e1a115847ad36449b0015864 SP:Homo sapiens @SQ SN:13 LN:115169878 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:283f8d7892baa81b510a015719ca7b0b SP:Homo sapiens @SQ SN:14 LN:107349540 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:98f3cae32b2a2e9524bc19813927542e SP:Homo sapiens @SQ SN:15 LN:102531392 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:e5645a794a8238215b2cd77acb95a078 SP:Homo sapiens @SQ SN:16 LN:90354753 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:fc9b1a7b42b97a864f56b348b06095e6 SP:Homo sapiens @SQ SN:17 LN:81195210 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:351f64d4f4f9ddd45b35336ad97aa6de SP:Homo sapiens @SQ SN:18 LN:78077248 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:b15d4b2d29dde9d3e4f93d1d0f2cbc9c SP:Homo sapiens @SQ SN:19 LN:59128983 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:1aacd71f30db8e561810913e0b72636d SP:Homo sapiens @SQ SN:20 LN:63025520 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:0dec9660ec1efaaf33281c0d5ea2560f SP:Homo sapiens @SQ SN:21 LN:48129895 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:2979a6085bfe28e3ad6f552f361ed74d SP:Homo sapiens @SQ SN:22 LN:51304566 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:a718acaa6135fdca8357d5bfe94211dd SP:Homo sapiens @SQ SN:X LN:155270560 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:7e0e2e580297b7764e31dbc80c2540dd SP:Homo sapiens @SQ SN:Y LN:59373566 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:1e86411d73e6f00a10590f976be01623 SP:Homo sapiens @SQ SN:MT LN:16569 UR:/lustre/scratch110/srpipe/references/Homo_sapiens/CGP_GRCh37.NCBI.allchr_MT/all/fasta/Homo_sapiens.GRCh37.NCBI.allchr_MT.fa AS:CGP GRCh37.NCBI.allchr_MT M5:c68f52674c9fb33aef52dcf399755519 SP:Homo sapiens