Table 3.

Top 30 spectral regions and their contributing metabolites identified by both sets of ML analysis given in descending order of importance along with their statistical analysis.

Group 1: Glioma vs Control
ML Analysis			Statistical Validation
Feature	Importance	Corresponding metabolite	p-value	log2(FC)
Model: Logistics Regression
1.47	1.0	Alanine	<0.0001	–3.7744
Model: Extra Tree Classifier
2.55	0.0642	β-Alanine	<0.0001	−2.5717
2.12	0.0524	Methionine	<0.0001	−3.3458
3.1	0.0491	Phenylalanine	<0.0001	−7.3967
3.07	0.0415	X	<0.0001	−2.5445
2.69	0.0405	NAA	<0.0001	−4.7668
1.47	0.0383	Alanine	<0.0001	−3.7744
0.98	0.0299	Valine	<0.0001	−2.7959
1.71	0.028	Leucine	<0.0001	−3.5926
3.13	0.025	Glutathione	0.0013	−5.7592
2.45	0.0222	Glutamine	<0.0001	−3.0169
1.88	0.022	GABA	0.0028	−1.1886
3.95	0.0204	Serine	0.0003	−2.4757
3.16	0.0182	Alanine	<0.0001	−5.5148
3.69	0.0179	α-glucose	<0.0001	−1.3382
1.44	0.0175	Deoxycholic acid	<0.0001	10.114
3.18	0.0168	Taurocholic acid	<0.0001	−4.2704
4.11	0.0161	Lactate	<0.0001	2.7555
1.72	0.0157	Arginine	0.0003	−2.6918
3.58	0.0149	Threonine	<0.0001	−6.6301
2.35	0.0148	Glutamate	0.0022	−1.4198
3.94	0.0143	Serine	<0.0001	−2.3249
3.14	0.014	Spermidine	0.0119	−4.8047
3.88	0.014	Aspartic acid	<0.0001	1.5565
2.09	0.0133	Glutamate	<0.0001	−1.859
3.21	0.0126	N-Acetylcholine	0.0004	−4.3221
1.04	0.0126	Valine	<0.0001	−1.8092
1.01	0.0124	Isoleucine	0.0002	3.8182
1.89	0.0121	GABA	0.001	−2.2659
3.68	0.0118	α-glucose	<0.0001	4.8319
1.99	0.0117	Isoleucine	0.0006	−1.2174
Model: Random Forest
2.12	0.0491	Methionine	<0.0001	−3.3458
0.98	0.0488	Valine	<0.0001	−2.7959
3.16	0.0438	Alanine	<0.0001	−5.5148
4.11	0.0344	Lactate	<0.0001	2.7555
1.47	0.0316	Alanine	<0.0001	−3.7744
3.53	0.03	Myoinositol	0.0003	1.0134
1.45	0.025	Isoleucine	0.0002	2.9475
1.44	0.0209	Deoxycholic acid	<0.0001	10.114
1.99	0.0195	Isoleucine	0.0006	−1.2174
2.69	0.019	NAA	<0.0001	−4.7668
2.32	0.0172	Glutamate	0.0003	2.1726
2.13	0.0172	Glutamine	<0.0001	−3.4879
2.45	0.0165	Glutamine	<0.0001	−3.0169
3.66	0.0157	Isoleucine	0.0050	4.9598
3.72	0.015	β-glucose	0.3716	NA
1.3	0.0146	Fatty acids	<0.0001	−1.3971
3.94	0.0144	Serine	<0.0001	−2.3249
3.69	0.0142	α-glucose	<0.0001	−1.3382
1.01	0.0142	Isoleucine	0.0002	3.8182
0.92	0.0139	Isoleucine	0.0002	2.3071
2.09	0.0133	Glutamate	<0.0001	−1.859
3.88	0.0117	Aspartate	<0.0001	1.5565
3.59	0.0114	L-Valine	0.001‘	−6.9614
Age	0.0107	NA	NA	NA
1.17	0.0105	X	0.006	−2.41
1.88	0.0105	GABA	0.0028	−1.1886
3.46	0.0097	β-glucose	0.0178	NA
3.22	0.0093	Arginine	0.0191	NA
3.58	0.0091	Threonine	<0.0001	−6.6301
3.47	0.0084	β-glucose	0.7007	NA
Group 2: LGG vs HGG
ML Analysis			Statistical Validation
Feature	Importance	Corresponding metabolite	p-value	log2(FC)
Model: Logistics Regression
3.51	0.2059	Choline	0.030	NA
2.01	0.1116	NAA	0.041	1.239
3.2	0.0719	P-Choline	0.127	NA
1.02	0.0531	Valine	0.040	NA
3.48	0.0523	β-Glucose	0.040	NA
2.39	0.0442	Succinate/Malate	0.040	−1.1293
1.68	0.0441	L-Arginine	0.227	1.678
1.82	0.0435	X	0.015	1.4804
2.4	0.0416	Succinate	0.092	NA
2.31	0.0386	X	0.207	−1.647
3.5	0.0324	NAA	0.133	−2.3824
2.3	0.0311	GABA	0.133	−3.0367
1.84	0.026	X	0.054	1.6947
3.53	0.026	Myoinositol	0.871	NA
1.26	0.0236	Isoleucine	0.064	−2.4499
1.99	0.0171	Isoleucine	0.039	NA
2.45	0.0156	L-Glutamine	0.195	NA
0.88	0.015	Fatty acid	0.239	−2.0748
3.91	0.0149	Creatine	0.054	1.2722
1.21	0.0125	X	0.054	3.6568
2.25	0.0122	Fatty acid	0.206	2.6199
0.9	0.012	Fatty acid	0.041	1.6497
3.26	0.0028	Taurine	0.009	1.1339
1.83	0	X	0.388	−1.791
1.63	0	X	0.195	NA
1.86	0	GABA	0.206	1.9942
1.97	0	Isoleucine	0.182	1.679
1.47	0	Alanine	0.640	3.2255
1.87	0	GABA	0.195	NA
1.88	0	GABA	0.195	NA
Model: Extra Tree Classifier
3.6	0.0637	Valine	0.015	1.5337
1.82	0.0352	X	0.015	1.4804
2.5	0.0265	NAA	0.015	1.3842
1.4	0.0254	X	0.071	1.5535
2.4	0.0254	Succinate	0.092	1.1227
1.97	0.0247	Isoleucine	0.182	1.679
2.04	0.0244	Glutamate	0.030	1.4984
0.99	0.0237	Isoleucine	0.104	1.2242
2.53	0.0232	X	0.015	2.0478
3.26	0.0232	Taurine	0.009	1.1339
2.08	0.0211	Glutamate	0.036	NA
3.59	0.0207	Threonine	0.053	NA
0.91	0.0186	Fatty acids	0.011	1.6453
0.98	0.017	Valine	0.249	1.7767
1.99	0.0167	Isoleucine	0.039	1.429
0.9	0.0167	Fatty acids	0.041	1.6497
3.33	0.0164	Scyllo inositol	0.015	1.5207
2.43	0.0162	Glutamine	0.222	NA
1.22	0.016	X	0.103	NA
3.91	0.0159	Creatine	0.054	1.2722
2.72	0.0154	NAA	0.136	2.2715
2.84	0.0149	X	0.054	1.2673
3.51	0.0144	Choline	0.030
0.85	0.0143	Tauro-cholicacid	0.726	−1.0208
1.68	0.0137	Leucine	0.227	1.678
3.54	0.0131	Glycine	0.050	1.1865
1.36	0.0127	Fatty acids	0.519	NA
3.42	0.0124	Taurine/Proline	0.031	NA
1.05	0.0123	Valine	0.097	1.5722
2.32	0.0119	Glutamate	0.026	NA
Model: Random Forest
3.6	0.0637	Valine	0.015	1.5337
1.82	0.0352	X	0.015	1.4804
2.5	0.0265	NAA	0.015	1.3842
1.4	0.0254	X	0.071	1.5535
2.4	0.0254	Succinate	0.092	1.1227
1.97	0.0247	Isoleucine	0.182	1.679
2.04	0.0244	Glutamate	0.030	1.4984
0.99	0.0237	Isoleucine	0.104	1.2242
2.53	0.0232	X	0.015	2.0478
3.26	0.0232	Taurine	0.009	1.1339
2.08	0.0211	Glutamate	0.036	NA
3.59	0.0207	Threonine	0.053	NA
0.91	0.0186	Fatty acids	0.011	1.6453
0.98	0.017	Valine	0.249	1.7767
1.99	0.0167	Isoleucine	0.039	1.429
0.9	0.0167	Fatty acids	0.041	NA
3.33	0.0164	scyllo inositol	0.015	1.5207
2.43	0.0162	Glutamine	0.222	NA
1.22	0.016	X	0.103	NA
3.91	0.0159	Creatine	0.054	1.2722
2.72	0.0154	NAAG	0.136	2.2715
2.84	0.0149	X	0.054	1.2673
3.51	0.0144	Choline	0.030	NA
0.85	0.0143	Tauro-cholicacid	0.726	−1.0208
1.68	0.0137	Leucine	0.227	1.678
3.54	0.0131	Glycine	0.050	1.1865
1.36	0.0127	Fatty acids	0.519	NA
3.42	0.0124	Taurine/Proline	0.031	NA
1.05	0.0123	Valine	0.097	1.5722
2.32	0.0119	Glutamate	0.026	NA

Key used: NAA = N-Acetylaspartate; X = Unknown metabolite; NA = Not available.