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Micro RNAs (mi RNAs) are small noncoding RNA molecules about 22 nucleotides long which regulate gene expression post-transcriptionally, and play key roles in a wide range of biological processes.

Many lines of evidence indicate that several mi RNAs can work together to affect target genes in the same or different biological pathways [1,2,3].

Lactation is a complex process known to be controlled by various regulatory mechanisms, including mi RNAs [9,10].

The roles of mi RNAs in dairy lactation or mammary gland development have been investigated by several authors [11,12,13,14,15,16,17,18].

The GREEN and BLUE modules were significantly correlated (| 0.5) with both SCC and lactose.

Overall, this study uncovered regulatory networks in which mi RNAs interacted with each other to regulate lactation traits.

The scatter plots of enriched GO-terms for the GREEN, BLUE, RED and TURQUOISE modules are shown in , Table S2b).

The BLUE and TURQUOISE modules shared three most significantly enriched GO-terms, which were sensory perception of chemical stimulus, intracellular part and G-protein coupled receptor activity for biological process, cellular component and molecular function, respectively (Figures S2 and S4, and Table S2a,c).

mi R-18a, mi R-221/222 cluster, and transcription factors HOXA7, and NOTCH 3 and 4, are important for the regulation of lactose.

Moreover, every module is assigned an eigenvalue, which enables determination of the relationship (correlation) between modules and traits of interest.

The hub genes of each module points to the most active mi RNAs in each network, which are potentially the most important mi RNAs regulating the transcriptomic mechanisms underlying the traits.

The red square nodes are mi RNA members of the GREEN module, the blue round nodes are common predicted target genes for these mi RNAs, the yellow round The mi RNA members of the BLUE, GREEN, TURQUOISE and RED modules were predicted to target 3361, 1232, 4241 and 979 unique genes, respectively (Table S1a–d).

Many mi RNAs shared the same target genes, especially when they had the same seed region (Genes targeted by at least four mi RNAs in the (a) BLUE, (b) RED and (c) TURQUOISE modules.

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