#METABOLOMICS WORKBENCH Codreags00_20230112_121230 DATATRACK_ID:3689 STUDY_ID:ST002442 ANALYSIS_ID:AN003979 PROJECT_ID:PR001573
VERSION             	1
CREATED_ON             	January 13, 2023, 8:05 am
#PROJECT
PR:PROJECT_TITLE                 	Alterations in CSF Urea Occur in Late Manifest Stage Huntington Disease
PR:PROJECT_TYPE                  	Untargeted Metabolomics analysis
PR:PROJECT_SUMMARY               	Huntington Disease (HD) is a neurodegenerative disorder caused by expanded
PR:PROJECT_SUMMARY               	cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the
PR:PROJECT_SUMMARY               	production of mutant huntingtin proteins (mHTT). Previous research has
PR:PROJECT_SUMMARY               	identified urea as a key metabolite elevated in HD animal models and post-mortem
PR:PROJECT_SUMMARY               	tissues of HD patients. The exact timing of these elevations in urea and the
PR:PROJECT_SUMMARY               	molecular mechanism(s) responsible for these disturbances remain unknown. To
PR:PROJECT_SUMMARY               	better understand the pathophysiologic mechanisms responsible for elevations in
PR:PROJECT_SUMMARY               	urea in HD, we completed a global metabolomic profile of cerebrospinal fluid
PR:PROJECT_SUMMARY               	(CSF) from individuals who were at several stages of disease: pre-manifest
PR:PROJECT_SUMMARY               	(PRE), manifest (MAN), and late-manifest (LATE) HD participants compared to
PR:PROJECT_SUMMARY               	controls. We found approximately 500 metabolites were significantly altered in
PR:PROJECT_SUMMARY               	pre-manifest participants compared to controls, although no significant
PR:PROJECT_SUMMARY               	difference in CSF urea or urea metabolites. Interestingly, CSF urea was only
PR:PROJECT_SUMMARY               	significantly elevated in LATE participants compared to controls. There were no
PR:PROJECT_SUMMARY               	changes in the urea metabolites, citrulline, ornithine and arginine throughout
PR:PROJECT_SUMMARY               	disease; however, we did observe changes in acetate, creatinine,
PR:PROJECT_SUMMARY               	4-acetamidobutanoate and 4-aminobutyraldehyde which are indirect modifiers of
PR:PROJECT_SUMMARY               	urea. Overall, our study confirms that elevations in urea do occur in HD, albeit
PR:PROJECT_SUMMARY               	later in disease and that these changes may reflect more central impairments to
PR:PROJECT_SUMMARY               	cellular energy metabolism yet to be explored.
PR:INSTITUTE                     	Vanderbilt University
PR:DEPARTMENT                    	Chemistry
PR:LABORATORY                    	Center for Innovative Technology
PR:LAST_NAME                     	CODREANU
PR:FIRST_NAME                    	SIMONA
PR:ADDRESS                       	1234 STEVENSON CENTER LANE
PR:EMAIL                         	SIMONA.CODREANU@VANDERBILT.EDU
PR:PHONE                         	6158758422
#STUDY
ST:STUDY_TITLE                   	Alterations in CSF Urea Occur in Late Manifest Stage Huntington Disease
ST:STUDY_TYPE                    	untargeted metabolomics analysis
ST:STUDY_SUMMARY                 	Huntington Disease (HD) is a neurodegenerative disorder caused by expanded
ST:STUDY_SUMMARY                 	cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the
ST:STUDY_SUMMARY                 	production of mutant huntingtin proteins (mHTT). Previous research has
ST:STUDY_SUMMARY                 	identified urea as a key metabolite elevated in HD animal models and post-mortem
ST:STUDY_SUMMARY                 	tissues of HD patients. The exact timing of these elevations in urea and the
ST:STUDY_SUMMARY                 	molecular mechanism(s) responsible for these disturbances remain unknown. To
ST:STUDY_SUMMARY                 	better understand the pathophysiologic mechanisms responsible for elevations in
ST:STUDY_SUMMARY                 	urea in HD, we completed a global metabolomic profile of cerebrospinal fluid
ST:STUDY_SUMMARY                 	(CSF) from individuals who were at several stages of disease: pre-manifest
ST:STUDY_SUMMARY                 	(PRE), manifest (MAN), and late-manifest (LATE) HD participants compared to
ST:STUDY_SUMMARY                 	controls. We found approximately 500 metabolites were significantly altered in
ST:STUDY_SUMMARY                 	pre-manifest participants compared to controls, although no significant
ST:STUDY_SUMMARY                 	difference in CSF urea or urea metabolites. Interestingly, CSF urea was only
ST:STUDY_SUMMARY                 	significantly elevated in LATE participants compared to controls. There were no
ST:STUDY_SUMMARY                 	changes in the urea metabolites, citrulline, ornithine and arginine throughout
ST:STUDY_SUMMARY                 	disease; however, we did observe changes in acetate, creatinine,
ST:STUDY_SUMMARY                 	4-acetamidobutanoate and 4-aminobutyraldehyde which are indirect modifiers of
ST:STUDY_SUMMARY                 	urea. Overall, our study confirms that elevations in urea do occur in HD, albeit
ST:STUDY_SUMMARY                 	later in disease and that these changes may reflect more central impairments to
ST:STUDY_SUMMARY                 	cellular energy metabolism yet to be explored.
ST:INSTITUTE                     	Vanderbilt University
ST:DEPARTMENT                    	Chemistry
ST:LABORATORY                    	Center for Innovative Technology
ST:LAST_NAME                     	CODREANU
ST:FIRST_NAME                    	SIMONA
ST:ADDRESS                       	1234 STEVENSON CENTER LANE
ST:EMAIL                         	SIMONA.CODREANU@VANDERBILT.EDU
ST:PHONE                         	6158758422
ST:NUM_GROUPS                    	4
ST:TOTAL_SUBJECTS                	60
#SUBJECT
SU:SUBJECT_TYPE                  	Human
SU:SUBJECT_SPECIES               	Homo sapiens
SU:TAXONOMY_ID                   	9606
SU:GENDER                        	Male and female
#SUBJECT_SAMPLE_FACTORS:         	SUBJECT(optional)[tab]SAMPLE[tab]FACTORS(NAME:VALUE pairs separated by |)[tab]Raw file names and additional sample data
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C07_C_1_1	Genotype:CONTROL | sex:m | age:32	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C07_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D01_C_1_1	Genotype:CONTROL | sex:m | age:28	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D01_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D02_C_1_1	Genotype:CONTROL | sex:m | age:44	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D02_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D10_C_1_1	Genotype:CONTROL | sex:f | age:58	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D10_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E04_C_1_1	Genotype:CONTROL | sex:f | age:47	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E04_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F04_C_1_1	Genotype:CONTROL | sex:m | age:35	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F04_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F06_C_1_1	Genotype:CONTROL | sex:m | age:51	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F06_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F10_C_1_1	Genotype:CONTROL | sex:m | age:54	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F10_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G01_C_1_1	Genotype:CONTROL | sex:m | age:57	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G01_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G04_C_1_1	Genotype:CONTROL | sex:f | age:53	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G04_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G06_C_1_1	Genotype:CONTROL | sex:f | age:53	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G06_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G11_C_1_1	Genotype:CONTROL | sex:f | age:61	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G11_C_1_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D06_C_1_2	Genotype:CONTROL | sex:m | age:44	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D06_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D08_C_1_2	Genotype:CONTROL | sex:m | age:28	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D08_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D09_C_1_2	Genotype:CONTROL | sex:m | age:32	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D09_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E11_C_1_2	Genotype:CONTROL | sex:f | age:47	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E11_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E12_C_1_2	Genotype:CONTROL | sex:f | age:59	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E12_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F01_C_1_2	Genotype:CONTROL | sex:f | age:53	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F01_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F05_C_1_2	Genotype:CONTROL | sex:m | age:36	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F05_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G03_C_1_2	Genotype:CONTROL | sex:m | age:54	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G03_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G05_C_1_2	Genotype:CONTROL | sex:m | age:57	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G05_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G07_C_1_2	Genotype:CONTROL | sex:f | age:54	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G07_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G09_C_1_2	Genotype:CONTROL | sex:f | age:61	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G09_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F12_C_1_2	Genotype:CONTROL | sex:m | age:51	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F12_C_1_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A03_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:48	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A03_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B02_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:36	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B02_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B03_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:30	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B03_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B04_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:33	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B04_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B05_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:29	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B05_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B07_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:35	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B07_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C05_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:33	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C05_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C11_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:36	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C11_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D11_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:42	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D11_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E01_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:30	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E01_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E02_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:48	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E02_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E03_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:43	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E03_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E08_HD_2_1	Genotype:PRE-MANIFEST | sex:m | age:31	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E08_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F11_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:42	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F11_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G10_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:26	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G10_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_H02_HD_2_1	Genotype:PRE-MANIFEST | sex:f | age:40	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_H02_HD_2_1
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A04_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:31	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A04_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A12_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:48	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A12_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B06_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:29	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B06_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B08_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:36	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B08_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B09_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:30	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B09_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B12_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:35	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B12_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C01_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:33	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C01_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C08_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:33	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C08_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C10_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:37	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C10_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C12_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:40	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C12_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D12_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:42	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D12_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E05_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:48	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E05_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E06_HD_2_2	Genotype:PRE-MANIFEST | sex:m | age:30	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E06_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E10_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:43	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E10_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F02_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:42	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F02_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_H03_HD_2_2	Genotype:PRE-MANIFEST | sex:f | age:26	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_H03_HD_2_2
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A02_HD_3	Genotype:EARLY MANIFEST | sex:f | age:57	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A02_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A05_HD_3	Genotype:EARLY MANIFEST | sex:m | age:49	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A05_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A07_HD_3	Genotype:EARLY MANIFEST | sex:m | age:35	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A07_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A08_HD_3	Genotype:EARLY MANIFEST | sex:m | age:56	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A08_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B10_HD_3	Genotype:EARLY MANIFEST | sex:f | age:48	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B10_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C04_HD_3	Genotype:EARLY MANIFEST | sex:m | age:39	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C04_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C09_HD_3	Genotype:EARLY MANIFEST | sex:m | age:59	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C09_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D05_HD_3	Genotype:EARLY MANIFEST | sex:m | age:41	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D05_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F03_HD_3	Genotype:EARLY MANIFEST | sex:f | age:52	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F03_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F07_HD_3	Genotype:EARLY MANIFEST | sex:f | age:41	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F07_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F09_HD_3	Genotype:EARLY MANIFEST | sex:f | age:59	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F09_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G02_HD_3	Genotype:EARLY MANIFEST | sex:f | age:59	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G02_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G08_HD_3	Genotype:EARLY MANIFEST | sex:m | age:46	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G08_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_G12_HD_3	Genotype:EARLY MANIFEST | sex:f | age:50	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_G12_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_H01_HD_3	Genotype:EARLY MANIFEST | sex:f | age:47	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_H01_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_H04_HD_3	Genotype:EARLY MANIFEST | sex:f | age:60	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_H04_HD_3
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A01_HD_4	Genotype:LATE MANIFEST | sex:f | age:38	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A01_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A06_HD_4	Genotype:LATE MANIFEST | sex:m | age:58	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A06_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A09_HD_4	Genotype:LATE MANIFEST | sex:m | age:66	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A09_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A10_HD_4	Genotype:LATE MANIFEST | sex:m | age:46	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A10_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_A11_HD_4	Genotype:LATE MANIFEST | sex:m | age:60	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_A11_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B01_HD_4	Genotype:LATE MANIFEST | sex:f | age:58	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B01_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_B11_HD_4	Genotype:LATE MANIFEST | sex:f | age:65	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_B11_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C02_HD_4	Genotype:LATE MANIFEST | sex:f | age:47	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C02_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C03_HD_4	Genotype:LATE MANIFEST | sex:f | age:57	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C03_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_C06_HD_4	Genotype:LATE MANIFEST | sex:f | age:55	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_C06_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D03_HD_4	Genotype:LATE MANIFEST | sex:m | age:51	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D03_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D04_HD_4	Genotype:LATE MANIFEST | sex:m | age:47	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D04_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_D07_HD_4	Genotype:LATE MANIFEST | sex:m | age:69	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_D07_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E07_HD_4	Genotype:LATE MANIFEST | sex:m | age:63	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E07_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_E09_HD_4	Genotype:LATE MANIFEST | sex:f | age:72	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_E09_HD_4
SUBJECT_SAMPLE_FACTORS           	-	SC_20201109_HILICp_FMS_CSF_F08_HD_4	Genotype:LATE MANIFEST | sex:m | age:60	RAW_FILE_NAME=SC_20201109_HILICp_FMS_CSF_F08_HD_4
#COLLECTION
CO:COLLECTION_SUMMARY            	CSF samples were collected from 60 participants as part of the CHDI HD-Clarity
CO:COLLECTION_SUMMARY            	study. There were 16 PRE, 16 MAN, 16 LATE HD participants and 12 control
CO:COLLECTION_SUMMARY            	participants. Disease stage was determined using the diagnostic confidence level
CO:COLLECTION_SUMMARY            	(DCL), length of CAG expansion and burden of pathology calculated from (CAG
CO:COLLECTION_SUMMARY            	expansion – 35.5) x Age. Control participants were individuals without a known
CO:COLLECTION_SUMMARY            	history of Huntington Disease (HD). All HD participants have a CAG expansion of
CO:COLLECTION_SUMMARY            	> 40. PRE participants were not motor manifest as indicated by a DCL of <4 and a
CO:COLLECTION_SUMMARY            	burden of pathology of > 250. MAN participants had a DCL =4 and a total
CO:COLLECTION_SUMMARY            	functional capacity (TFC) between 7-13. The LATE group had all the above
CO:COLLECTION_SUMMARY            	criteria for MAN and a TFC score between 0-6. Repeat CSF and blood samples
CO:COLLECTION_SUMMARY            	collected 4-8 weeks after a baseline (BL) visit are provided for all control and
CO:COLLECTION_SUMMARY            	PRE participants. Participants’ age and gender are reported here. Three
CO:COLLECTION_SUMMARY            	participants (2 PRE, 1 MAN) were taking supplemental vitamins; however, their
CO:COLLECTION_SUMMARY            	metal levels were similar to those in their corresponding participant group and
CO:COLLECTION_SUMMARY            	thus, the data from these participants are included. Basic demographics like age
CO:COLLECTION_SUMMARY            	and gender were reported previously in addition to participants' scores on a
CO:COLLECTION_SUMMARY            	battery of cognitive, behavioral and motor assessments including the symbol
CO:COLLECTION_SUMMARY            	digit modality test (SDMT), Stroop Word Reading (SWR), total functional capacity
CO:COLLECTION_SUMMARY            	(TFC), total motor score (TMS) and the recently developed cUHDRS.
CO:SAMPLE_TYPE                   	CSF
CO:STORAGE_CONDITIONS            	-80℃
#TREATMENT
TR:TREATMENT_SUMMARY             	No treatment
#SAMPLEPREP
SP:SAMPLEPREP_SUMMARY            	CSF samples collected were flash frozen and stored at -80°C until analyzed via
SP:SAMPLEPREP_SUMMARY            	Liquid ChromatographyHigh Resolution Mass Spectrometry (LC-HRMS and
SP:SAMPLEPREP_SUMMARY            	LC-HRMS/MS)-based metabolomics in the Vanderbilt Center for Innovative
SP:SAMPLEPREP_SUMMARY            	Technology (CIT) using previously described methods (cite). Briefly, equal
SP:SAMPLEPREP_SUMMARY            	volumes (100 µL) of previously frozen CSF was diluted with 100 µL ice-cold
SP:SAMPLEPREP_SUMMARY            	lysis buffer (1:1:2, Acetonitrile:MeOH:Ammonium Bicarbonate 0.1M, pH 8.0, LC-MS
SP:SAMPLEPREP_SUMMARY            	grade). Addition of isotopically labeled phenylalanine-D8 and biotin-D2 were
SP:SAMPLEPREP_SUMMARY            	added to individual samples prior to protein precipitation by addition of 800
SP:SAMPLEPREP_SUMMARY            	µL of ice-cold methanol. Following overnight incubation at -80°C, precipitated
SP:SAMPLEPREP_SUMMARY            	proteins were pelleted by centrifugation at 10,000 rpm for 10 min and metabolite
SP:SAMPLEPREP_SUMMARY            	extracts were dried down in vacuo and stored at -80°C until reconstitution
SP:SAMPLEPREP_SUMMARY            	prior to MS analysis.
#CHROMATOGRAPHY
CH:CHROMATOGRAPHY_SUMMARY        	CSF extracts (5uL injection volume) were separated on an ACQUITY UPLC BEH Amide
CH:CHROMATOGRAPHY_SUMMARY        	HILIC 1.7μm, 2.1 × 100 mm column (Waters Corporation, Milford, MA) held at
CH:CHROMATOGRAPHY_SUMMARY        	30°C as previously described (cite). Briefly, liquid chromatography was
CH:CHROMATOGRAPHY_SUMMARY        	performed at 200 µL min−1 using solvent A (5 mM ammonium formate in 90%
CH:CHROMATOGRAPHY_SUMMARY        	water, 10% acetonitrile and 0.1% formic acid) and solvent B (5 mM ammonium
CH:CHROMATOGRAPHY_SUMMARY        	formate in 90% acetonitrile, 10% water and 0.1% formic acid) with a gradient
CH:CHROMATOGRAPHY_SUMMARY        	length of 30 min.
CH:CHROMATOGRAPHY_TYPE           	HILIC
CH:INSTRUMENT_NAME               	Thermo Vanquish
CH:COLUMN_NAME                   	Waters ACQUITY UPLC BEH HILIC (100 x 2.1mm,1.7um)
CH:SOLVENT_A                     	90% water, 10% acetonitrile, 5mM Ammonium Formate, 0.1%FA
CH:SOLVENT_B                     	10% water, 90% acetonitrile, 5mM Ammonium Formate, 0.1%FA
CH:FLOW_GRADIENT                 	30 min
CH:FLOW_RATE                     	0.20mL/min
CH:COLUMN_TEMPERATURE            	30
#ANALYSIS
AN:ANALYSIS_TYPE                 	MS
#MS
MS:INSTRUMENT_NAME               	Thermo Q Exactive HF hybrid Orbitrap
MS:INSTRUMENT_TYPE               	Orbitrap
MS:MS_TYPE                       	ESI
MS:ION_MODE                      	POSITIVE
MS:MS_COMMENTS                   	Full MS analyses were acquired over the mass-to-charge ratio (m/z) range of
MS:MS_COMMENTS                   	70-1,050 in positive ion mode. Full mass scan was acquired at 120,000 resolution
MS:MS_COMMENTS                   	with a scan rate of 3.5 Hz, automatic gain control (AGC) target of 1x106, and
MS:MS_COMMENTS                   	maximum ion injection time of 100 ms, and MS/MS spectra were collected at 15,000
MS:MS_COMMENTS                   	resolution, AGC target of 2x105 ions, with a maximum ion injection time of 100
MS:MS_COMMENTS                   	ms
MS:MS_RESULTS_FILE               	ST002442_AN003979_Results.txt	UNITS:time_m/z	Has m/z:Yes	Has RT:Yes	RT units:Minutes
#END