Mean Hes score. Threshold

Transcription

1 Mean Hes score Common 0.08 Family Threshold SUPPLEMENTARY FIG. 1. Trend of mean Hes scores calculated based on the corresponding threshold. Blue line denotes the trend of the mean Hes scores calculated based on the corresponding threshold for common mirnas between different datasets. Red line denotes the trend of the mean Hes scores calculated based on the corresponding threshold for mirnas belonging to the same family between different datasets. Supplementary Table 1. The Number of Similar GO Form Pairs Based on Different Threshold Threshold CC MF BP 0 144, ,116 3,969, , ,994 1,287, , , , ,103 55, , ,878 33, , ,854 17, , ,856 9,392 57, ,195 4,723 27, ,170 2,216 12, , We performed GO term similarity for all terms in CC, MF, and BP. We listed the number of similarity GO term pairs based on threshold 0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, and 1.0 (as listed in the following table). The numbers of enriched GO terms were CC 543, MF 1296, and BP 2,824, respectively. The suitable threshold should not import GO terms more than the actual number. We doubled the number of enriched GO terms (resulting in CC 1,086, MF 2,592, and BP 5,648) and found that under the threshold 0.8, the number of the three parts were most similar to this number.

2 Hos Hos_family Hos_S Hos_family_S 0.5 Mean Hos value Threshold SUPPLEMENTARY FIG. 2. Trend of the mean Hos scores calculated based on the corresponding threshold. Blue line denotes the trend of the mean Hos scores calculated based on the corresponding threshold for common mirnas between different datasets. Red line denotes the trend of the mean Hos scores calculated based on the corresponding threshold for mirnas belonging to the same family between different datasets % % 50% Percentage 40% 30% 20% 10% 0% 0.21% ALL mir_ts mir_pt4 PT5_RNA22 DT_PT4 PT4_TS Comparison pairs SUPPLEMENTARY FIG. 3. Distribution of Hos scores based on the same function. The three Hos bins were presented by different colors as follows: [0, 0.06) (black); [0.06, 0.2) (red); [0.2, 1.0] (blue). The heights of the bars exhibit the percentages for each bin in each comparison pair. The comparison (marked All ) represented the distribution of Hos scores for all mirnas.

3 Target MF BP GO MF_S BP_S CC CC_S I Value Comparison levels SUPPLEMENTARY FIG. 4. I value of mirna families on eight comparison levels. The distribution of the I value for mirna families was presented in a series of boxes. Each box stood for a comparison level based on which the I value was computed. MF_S, BP_S, and CC_S refers to the corresponding I values that were based on a similar function.

4 Supplementary Table 2. Similarity Between Algorithms Based on mirnas with the Same Name Database Program Target GO BP MF CC BP_S MF_S CC_S mirgen Miranda(microrna.org) mirgen mirgen Union mirgen miranda(mirbase) mirgen microrna.org mirgen PicTar4 &&TargetScans mirgen TargetScans mirgen miranda(mirbase) mirgen PicTar4 &&TargetScans mirnamap mirgen miranda(org)&pictar4&targetscans mirnamap TargetScan mirnamap TargetScan mirgen miranda(org)&pictar4&targetscans Rna22 (continued)

5 Supplementary Table 2 Similarity Between Algorithms Based on mirnas in the Same Family (Continued) Database Program Target GO BP MF CC BP_S MF_S CC_S mirgen DIANA-microT mirgen union mirgen mirgen Union mirgen miranda(mirbase) mirgen microrna.org mirgen PicTar4 &&TargetScans H mirgen TargetScans mirgen PicTar4 &&TargetScans mirgen miranda(mirbase) mirnamap mirgen miranda(org)&pictar4&targetscans mirnamap TargetScan (continued)

6 Supplementary Table 2. (Continued) Database Program Target GO BP MF CC BP_S MF_S CC_S mirgen miranda(org)&pictar4&targetscans mirnamap TargetScan mirgen DIANA-microT Rna22 mirgen DIANA-microT

7 Supplementary Table 3. Enriched GO Terms of Targets GO Term ID Level Name Description 1 Enriched BP terms GO: adenyl ribonucleotide binding Interacting selectively with an adenyl ribonucleotide, any compound consisting of adenosine esterified with (ortho)phosphate or an oligophosphate at any hydroxyl group on the ribose moiety. GO: zinc ion binding Interacting selectively with zinc (Zn) ions. GO: protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein þ ATP ¼ a phosphoprotein þ ADP. GO: pyrophosphatase activity Catalysis of the hydrolysis of a pyrophosphate bond between two phosphate groups, leaving one phosphate on each of the two fragments. GO: transcription coactivator activity The function of a transcription cofactor that activates transcription from a RNA polymerase II promoter; does not bind DNA itself. GO: ATP binding Interacting selectively with ATP, adenosine 5 -triphosphate, a universally important coenzyme and enzyme regulator. GO: nucleosidetriphosphatase activity Catalysis of the reaction: a nucleoside triphosphate þ H 2 O ¼ nucleoside diphosphate þ phosphate. GO: protein serine/ threonine kinase activity Catalysis of the reaction: ATP þ a protein serine/ threonine ¼ ADP þ protein serine/threonine phosphate. GO: ATPase activity Catalysis of the reaction: ATP þ H2O ¼ ADP þ phosphate. May or may not be coupled to another reaction. GO: ATP-dependent helicase activity Catalysis of the reaction: ATP þ H2O ¼ ADP þ phosphate to drive the unwinding of a DNA or RNA helix. 2 Enriched MF terms GO: RNA biosynthetic process GO: regulation of transcription GO: protein modification process The chemical reactions and pathways resulting in the formation of RNA, ribonucleic acid, one of the two main type of nucleic acid, consisting of a long, unbranched macromolecule formed from ribonucleotides joined in 3,5 -phosphodiester linkage. Includes polymerization of ribonucleotide monomers. Any process that modulates the frequency, rate, or extent of the synthesis of either RNA on a template of DNA or DNA on a template of RNA. The covalent alteration of one or more amino acids occurring in proteins, peptides, and nascent polypeptides (cotranslational, posttranslational modifications). Includes the modification of charged trnas that are destined to occur in a protein (pretranslation modification). GO: transcription The synthesis of either RNA on a template of DNA or DNA on a template of RNA. GO: RNA processing Any process involved in the conversion of one or more primary RNA transcripts into one or more mature RNA molecules. GO: small GTPase mediated signal transduction GO: posttranslational protein modification GO: regulation of transcription, DNA-dependent GO: transcription, DNAdependent GO: transcription from RNA polymerase II promoter Any series of molecular signals in which a small monomeric GTPase relays one or more of the signals. The covalent alteration of one or more amino acids occurring in a protein after the protein has been completely translated and released from the ribosome. Any process that modulates the frequency, rate, or extent of DNAdependent transcription. The synthesis of RNA on a template of DNA. The synthesis of RNA from a DNA template by RNA polymerase II (Pol II), originating at a Pol II-specific promoter. Includes transcription of messenger RNA (mrna) and certain small nuclear RNAs (snrnas). 3 Enriched CC terms GO: cell junction A plasma membrane part that forms a specialized region of connection between two cells or between a cell and the extracellular matrix. At a cell junction, anchoring proteins extend through the plasma membrane to link cytoskeletal proteins in one cell to cytoskeletal proteins in neighboring cells or to proteins in the extracellular matrix. (continued)

8 Supplementary Table 3. (Continued) GO Term ID Level Name Description GO: cytoplasmic part Any constituent part of the cytoplasm, all of the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures GO: intracellular membraneenclosed organelle GO: intracellular nonmembranebounded organelle GO: intrinsic to plasma membrane Organized structure of distinctive morphology and function, bounded by a single or double lipid bilayer membrane and occurring within the cell. Includes the nucleus, mitochondria, plastids, vacuoles, and vesicles. Excludes the plasma membrane. Organized structure of distinctive morphology and function, not bounded by a lipid bilayer membrane and occurring within the cell. Includes ribosomes, the cytoskeleton, and chromosomes. Located in the plasma membrane such that some covalently attached portion of the gene product, for example, part of a peptide sequence or some other covalently attached moiety such as a GPI anchor, spans, or is embedded in one or both leaflets of the membrane. GO: nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell s chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. GO: cytoplasmic vesicle A vesicle formed of membrane or protein, found in the cytoplasm of a cell. GO: cytoskeleton Any of the various filamentous elements that form the internal framework of cells, and typically remain after treatment of the cells with mild detergent to remove membrane constituents and soluble components of the cytoplasm. The term embraces intermediate filaments, microfilaments, microtubules, the microtrabecular lattice, and other structures characterized by a polymeric filamentous nature and long-range order within the cell. The various elements of the cytoskeleton not only serve in the maintenance of cellular shape but also have roles in other cellular functions, including cellular movement, cell division, endocytosis, and movement of organelles. GO: Golgi apparatus A compound membranous cytoplasmic organelle of eukaryotic cells, consisting of flattened, ribosome-free vesicles arranged in a more or less regular stack. The Golgi apparatus differs from the endoplasmic reticulum in often having slightly thicker membranes, appearing in sections as a characteristic shallow semicircle so that the convex side (cis or entry face) abuts the endoplasmic reticulum, secretory vesicles emerging from the concave side (trans or exit face). In vertebrate cells there is usually one such organelle, while in invertebrates and plants, where they are known usually as dictyosomes, there may be several scattered in the cytoplasm. The Golgi apparatus processes proteins produced on the ribosomes of the rough endoplasmic reticulum; such processing includes modification of the core oligosaccharides of glycoproteins, and the sorting and packaging of proteins for transport to a variety of cellular locations. Three different regions of the Golgi are now recognized both in terms of structure and function: cis, in the vicinity of the cis face, trans, in the vicinity of the trans face, and medial, lying between the cis and trans regions. GO: integral to plasma membrane Penetrating at least one phospholipid bilayer of a plasma membrane. May also refer to the state of being buried in the bilayer with no exposure outside the bilayer. GO: mitochondrion A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. GO: Golgi apparatus part Any constituent part of the Golgi apparatus, a compound membranous cytoplasmic organelle of eukaryotic cells, consisting of flattened, ribosome-free vesicles arranged in a more or less regular stack. (continued)

9 Supplementary Table 3. (Continued) GO Term ID Level Name Description GO: microtubule cytoskeleton The part of the cytoskeleton (the internal framework of a cell) composed of microtubules and associated proteins. GO: mitochondrial part Any constituent part of a mitochondrion, a semiautonomous, selfreplicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. GO: nuclear part Any constituent part of the nucleus, a membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. GO: nuclear lumen The volume enclosed by the nuclear inner membrane. GO: nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus. GO: nucleoplasm part Any constituent part of the nucleoplasm, that part of the nuclear content other than the chromosomes or the nucleolus. GO: transcription factor complex Any complex, distinct from RNA polymerase, including one or more polypeptides capable of binding DNA at promoters or at cisacting regulatory sequences, and regulating transcription Similarity value Number of GO terms SUPPLEMENTARY FIG. 5. Trend of similarity values of the seven metrics for hsa-let-7d in a comparison pair to Rh-miR. In this figure, 1 7 denotes metrics named Simpson, Second Kulczynski, Ochiai/Otsuka, Dice, Jaccard, Sokal, and Sneath, and the Triparite Similarity Index based on Cost Functions respectively listed in Table 2.

10 25 Mean HHf score HHf HHf_s Threshold SUPPLEMENTARY FIG. 6. Trend of the mean HHf scores calculated based on the corresponding threshold. Blue line denotes the trend of the mean HHf scores calculated based on the corresponding threshold for common mirnas between different datasets. Red line denotes the trend of the mean HHf scores calculated based on the corresponding threshold for mirnas belonging to the same family between different datasets.