Carnelian uncovers hidden functional patterns across diverse study populations from whole metagenome sequencing reads

Table 1 Shared functional dysbiosis between two type 2 diabetes (T2D) cohorts and two Crohn’s disease (CD) cohorts

ID	Pathway	Carnelian	mi-faser	HUMAnN2	Kraken2	Fisher’s p (Carnelian)
(a) Common pathways between Chinese and European T2D cohorts
00030	Pentose phosphate pathway	SB	NB	NB	NB	6.59E −03
00040	Pentose and gluconerate interconversions	SB	NB	NB	NB	9.88E −03
00051	Fructose and mannose metabolism	SB	SE	NB	NB	4.94E −04
00052	Galactose metabolism	SB	NB	NB	NB	4.71E −03
00061	Fatty acid biosynthesis	SB	SC	NB	SC	6.56E −03
00190	Oxidative phosphorylation	SB	SE	SC	SE	4.97E −04
00250	Alanine, aspartate, and glutamate metabolism	SB	NB	NB	NB	1.48E −04
00290	Valine, leucine, and isoleucine biosynthesis	SB	SE	NB	NB	1.68E −05
00590	Arachidonic acid metabolism	SB	NB	NB	NB	2.11E −03
00600	Sphingolipid metabolism	SB	SE	NB	SC	8.86E −05
00730	Thiamine metabolism	SB	NB	NB	NB	2.62E −03
00983	Drug metabolism—other enzymes	SB	NB	NB	NB	2.62E −03
00195	Photosynthesis	SB	SB	SC	SB	2.74E −03
00254	Aflatoxin biosynthesis	SC	SC	NB	SB	1.03E −02
(b) Common pathways between US and Swedish CD cohorts
00500	Starch and sucrose metabolism	SB	NB	SS	SS	4.91E −06
00620	Pyruvate metabolism	SB	NB	NB	SS	4.05E −04
00640	Propanoate metabolism	SB	NB	NB	NB	9.04E −03
00290	Valine, leucine, and isoleucine biosynthesis	SB	SS	NB	SS	5.03E −03
00450	Selenocompound metabolism	SB	NB	NB	NB	8.95E −03
00460	Cyanoamino acid metabolism	SB	NB	SS	SS	8.33E −05
00513	Various types of N-glycan biosynthesis	SB	NB	NB	NB	5.79E −03
00710	Carbon fixation in photosynthetic organisms	SB	NB	NB	SS	1.09E −05
00410	Beta-alanine metabolism	NB	SS	NB	SB	5.79E −01

(a) Common pathways between Chinese and European T2D cohorts which have significantly altered read abundances. We found 13 shared pathways of which 12 are highly relevant to T2D; these pathways are significant in individual cohorts (BH-corrected Wilcoxon rank-sum test p value <0.05) as well as in Fisher’s combined test at p value <0.05 cutoff. On the other hand, mi-faser finds only the photosynthesis pathway and Kraken2 finds the photosynthesis and aflatoxin biosynthesis pathways to be commonly disrupted between both the cohorts; with HUMAnN2-profiles, no overlap at the pathway level was found (Additional file 2: Tables S11–S16). (b) Common pathways between the US and Swedish CD cohorts which have significantly altered read abundances. We identify shared dysbiosis in 8 pathways between the two study cohorts; these pathways are significant in individual cohorts as well as in Fisher’s combined test at p value <0.05 cutoff. On the other hand, only Kraken2 finds the beta-alanine metabolism pathway to be commonly disrupted between both the cohorts; with mi-faser- and HUMAnN2-profiles, no overlap at the pathway level was found (Additional file 3: Tables S23, S24, S27, S28, S31, and S32). SB significant in both the studies, NB detected but not significant in both the studies, SC significant in the Chinese cohort only, SE significant in European cohort only, SU significant in the US cohort only, SS significant in the Swedish cohort only

ISSN: 1474-760X