The total C value of each DE ncRNA is equal to the sum of BPvalue, CC value, MF value and KEGG value
We calculated the Cvalue of eachDE miRNA in skeletal muscledenervation, Alzheimer's disease, prostate cancer andgastric cancerdata setsrespectively.In addition, we calculate the C value of eachlncRNA in skeletal muscle denervation and adipocyte differentiationdata sets.Using the mathematical modelwe designed, the C values ofeach DE miRNA based on biological process (BP), cellular component(CC), molecular function (MF) and KEGG analysis can be obtained,and we call these C values as BP value, CC value, MF value and KEGGvalue respectively. The total C value of each DE miRNA is equal tothe sum of BP value, CC value, MF value and KEGG value. The DEmiRNAs were sorted with the total C value to obtain the 10 DEmiRNAs with maximum C value, named as top10 C value miRNAs (Table1-4). The top10 DE miRNAs with maximum absolute Log2 FC (top10 FCmiRNAs), and the top10 DE miRNAs with minimum P value (top10 Pvalue miRNAs), were obtained by sorting the DE miRNAs according tothe absolute Log2 fold FC and P value respectively(TableS1-8).Similarly, DE lncRNAs are processed in the same way to obtaintop5 C value lncRNAs, top5 FC lncRNAs, top5P value lncRNAs foradipocyte differentiation and top10 C value lncRNAs, top10 FClncRNAs, top10 P value lncRNAsfor skeletal muscle denervation.(Table S9-14).
Table 1
The top10miRNAs according to C valueinskeletal muscledenervation
miRNAs | KEGG value | BP value | CC value | MF value | C value |
mmu-miR-1943-5p | 33.22977743 | 816.2096329 | 57.79710246 | 86.48301468 | 993.7195275 |
mmu-miR-322-5p | 30.84058475 | 752.9168146 | 68.55345126 | 79.59753997 | 931.9083906 |
mmu-miR-497a-5p | 30.73416222 | 748.7865715 | 69.70753712 | 79.46588326 | 928.6941541 |
mmu-miR-674-5p | 27.16055299 | 715.4413807 | 58.01127153 | 72.71039755 | 873.3236028 |
mmu-miR-377-3p | 27.49012205 | 693.5040261 | 53.27285114 | 72.83266223 | 847.0996615 |
mmu-miR-378d | 23.25957428 | 680.9892711 | 61.28062951 | 72.28974851 | 837.8192234 |
mmu-miR-486a-3p | 26.82482408 | 657.0154824 | 50.6865571 | 69.48345827 | 804.0103219 |
mmu-miR-34a-5p | 26.69878945 | 659.2445359 | 53.42728799 | 63.0868827 | 802.457496 |
mmu-miR-34c-5p | 26.69878945 | 659.2445359 | 53.42728799 | 63.0868827 | 802.457496 |
mmu-miR-485-5p | 24.79976611 | 631.6503987 | 56.88385135 | 69.472899 | 782.8069152 |
BP, biological process;CC,cellularcomponent;MF, molecular function |
Table 2
The top10miRNAs according to C value inAlzheimer’s disease
miRNAs | KEGG value | BP value | CC value | MF value | C value |
mmu-miR-340-5p | 43.52080776 | 1010.03906 | 99.40722008 | 95.12478643 | 1248.091874 |
mmu-miR-128-3p | 32.34055348 | 702.2784936 | 72.03995682 | 72.09752374 | 878.7565277 |
mmu-miR-1912-3p | 31.48177854 | 665.3035883 | 71.02378772 | 65.40238219 | 833.2115368 |
mmu-miR-3065-5p | 28.57251324 | 635.0080827 | 59.73887501 | 60.19657486 | 783.5160458 |
mmu-miR-30e-5p | 25.07905102 | 603.9771948 | 61.33651101 | 55.31973524 | 745.712492 |
mmu-miR-30b-5p | 24.31969616 | 578.0747339 | 60.54628078 | 54.11557602 | 717.0562868 |
mmu-miR-369-3p | 21.98379268 | 578.5994009 | 50.71409202 | 53.23059546 | 704.5278811 |
mmu-miR-30f | 23.94953791 | 503.5940067 | 55.68167458 | 48.96495449 | 632.1901737 |
mmu-miR-16-5p | 24.36382475 | 493.9211057 | 47.41829077 | 46.52040221 | 612.2236234 |
mmu-miR-3470a | 18.44946604 | 405.6942042 | 42.64795188 | 40.23637553 | 507.0279976 |
BP, biological process; CC,cellularcomponent; MF, molecular function |
Table 3
The top10miRNAs according to C value inprostate cancer
miRNAs | KEGG value | BP value | CC value | MF value | C value |
hsa-miR-374a-5p | 4.398464287 | 118.2692853 | 5.213255954 | 10.04399186 | 137.9249974 |
hsa-miR-513a-5p | 5.657237644 | 112.0295308 | 6.910295123 | 12.59297097 | 137.1900346 |
hsa-miR-95-5p | 3.466944549 | 116.9227758 | 5.477859854 | 9.568881404 | 135.4364617 |
hsa-miR-374b-5p | 3.8075956 | 113.5989789 | 5.300186874 | 11.67343102 | 134.3801924 |
hsa-miR-498 | 4.728130359 | 107.2751254 | 5.824931497 | 10.83476997 | 128.6629573 |
hsa-miR-20a-5p | 4.115587199 | 109.1116054 | 5.632825474 | 8.080791708 | 126.9408098 |
hsa-miR-30e-5p | 3.611723927 | 102.8695362 | 5.273755273 | 8.075628363 | 119.8306438 |
hsa-miR-96-5p | 3.053742658 | 94.34293044 | 5.100190161 | 6.580687364 | 109.0775506 |
hsa-miR-148a-5p | 3.391802004 | 90.10482282 | 4.519060515 | 6.899577071 | 104.9152624 |
hsa-miR-429 | 3.2432555 | 85.75354374 | 5.037021005 | 7.643002043 | 101.6768223 |
BP, biological process; CC,cellularcomponent; MF, molecular function |
Table 4
The top10miRNAs according to C value ingastric cancer
miRNAs | KEGG value | BP value | CC value | MF value | C value |
hsa-miR-153-5p | 18.23914759 | 362.6949521 | 64.02355601 | 71.76595514 | 516.7236109 |
hsa-miR-3662 | 15.39458508 | 317.1733239 | 49.40052706 | 52.85782946 | 434.8262655 |
hsa-miR-548f-3p | 14.21781796 | 286.8668432 | 49.40872076 | 47.79869518 | 398.2920771 |
hsa-miR-5680 | 13.27934194 | 242.4315078 | 42.30706957 | 49.89122698 | 347.9091463 |
hsa-miR-944 | 14.78584485 | 239.0950535 | 40.7592345 | 49.77751375 | 344.4176466 |
hsa-miR-7-2-3p | 13.34378972 | 249.0496147 | 38.59579289 | 38.19653997 | 339.1857373 |
hsa-miR-4677-5p | 8.419400634 | 187.5755651 | 34.26195456 | 30.58636571 | 260.843286 |
hsa-miR-20a-5p | 7.557754765 | 178.5451401 | 36.14268786 | 28.25566276 | 250.5012455 |
hsa-miR-4728-5p | 10.00609667 | 161.1988844 | 32.79039421 | 31.1539595 | 235.1493347 |
hsa-miR-6507-5p | 10.37776368 | 162.008939 | 28.4527209 | 26.25126198 | 227.0906856 |
BP, biological process; CC,cellularcomponent; MF, molecular function |
C value is superior to log2 FC and P value in miRNAsoperation results
In each data set, the most significant enriched BP term, CCterm, MF term, KEGG pathway and the most involved BP term, CC term,MF term, KEGG pathway were obtained by DEmRNAs enrichmentanalysis.We took the intersections of DE mRNAs with the predictedtarget genes of top10 C value miRNAs, top10 FC miRNAs and top10 Pvalue miRNAs respectively, and then calculated the proportion ofthese intersections in the above pathways/terms. It was found thatthe proportion of top10 C Value miRNAs target mRNAs wassignificantly larger than that of top10 FC miRNAs, top10 P valuemiRNAs in the above terms/pathways (Fig.1). Furthermore, weenriched KEGG pathways based on DE mRNAs and pathways with p valueless than 0.01 to generate an annotation network (Fig.2). Accordingto the distance from the centre, the annotation network was dividedinto three regions: core region, subcore region, and non-coreregion (Fig. 2). In the annotation network, the predicted targetgenes of top10 C value miRNAs, top10 FC miRNAs and top10 p valuemiRNAs were labeled in red (Fig. S1). It was found that the totalnumber of top10 C value miRNAs’ target genes and their proportionin each region were larger than those of top10 FC miRNAs, and top10P value miRNAs (Fig.3).
Based on extensive literature, we identified 14 skeletal musclegrowth regulatory miRNAs, 6 Alzheimer’s disease associated miRNAs,7prostate cancer associated miRNAs, 6gastric cancer associatedmiRNAsand found that when DE miRNAs were sorted by C value, thesequence number accumulation value of thesemiRNAs was significantlysmaller than that of the other two indexes, which means that thesemiRNAs sequences increased integrally (Fig. 4). When sorting by Cvalue versus sorting by absolute Log2 FC/ P value, most of thedisease critical miRNAs ranked up(Fig. 4).
C value is superior to log2 FC and P value in lncRNAsoperation results
We got a conclusion similar to miRNA in the result of lncRNAoperation based on skeletal muscle denervation and adipocytedifferentiation data sets. In skeletal muscle denervationdata set,we calculated the proportion of the predicted target genes of top10C value lncRNAs, top10 FC lncRNAs, and top10 P value lncRNAs in the7 most enriched terms/pathways respectively, and found that theproportion of the genes regulated by top10 C value lncRNAs waslarger than that of top10 FC lncRNAs and top10 P value lncRNAs(Fig. 5A). Then, the predicted target genes of top10 C valuelncRNAs, top10 FC lncRNAs and top10 P value lncRNAs were labeled inred in KEGG annotation network(Fig. 5B-D). It was found that thetotal number of top10 C value lncRNAs’ target genes and theirproportion in each region (total: 87, core region: 17.9%, subcoreregion: 17%, non-core region: 19.7%) were larger than those oftop10 FC lncRNAs (total: 65, core region: 11.5%, subcore region:12.7%, non-core region: 16.9%), and top10 P value lncRNAs (total:61, core area: 10.3%, subcore area: 11.8%, non-core area: 16.9%)(Fig. 5E-F).
Since there are relatively few DElncRNAs and DE mRNAsinadipocyte differentiation data set, we take top5C value lncRNAs,top5 FC lncRNAs, top5 P value lncRNAs and draw the KEGG networkwithout partition (Fig. S2). The proportion of the genes regulatedby top5 C value lncRNAs was larger than that of top5 FC lncRNAs andtop5 P value lncRNAs in GO terms and KEGG annotation network (Fig.6A-B). And when DE lncRNAs were sorted by C value, theadipocytedifferentiation associatedlncRNAs sequences increased integrallythan that of the other two indexes (Fig. 6C-D).