|
NGS測序技術服務 DRIP-seq |
|
基因芯片技術服務 Small RNA修飾芯片 m6A單堿基分辨率芯片 mRNA&lncRNA表觀轉錄組芯片 circRNA表觀轉錄組芯片 |
NGS測序技術服務 RNA m6A甲基化測序（MeRIP Seq） |
LC-MS mRNA堿基修飾檢測 tRNA堿基修飾檢測 |
PCR技術服務 MeRIP-PCR技術服務 m6A絕對定量RT-PCR技術服務 m6A單堿基位點PCR（MazF酶切法）技術服務 |
|
基因芯片技術服務 DNA甲基化芯片 DNA羥甲基化芯片 ChIP-chip |
NGS測序技術服務 DNA甲?；奏?5fc)修飾測序 DNA 5hmC 測序（化學法） DNA甲基化測序 DNA羥甲基化測序 染色質免疫共沉淀測序 |
PCR技術服務 MeDIP-qPCR hMeDIP-qPCR ChIP-qPCR |
|
蛋白相對定量 TMT標記定量技術 非標定量技術 |
蛋白修飾 TMT標記定量磷酸化 非標定量磷酸化 |
RNA/蛋白-蛋白相互作用 RNA-蛋白相互作用 蛋白-蛋白相互作用 |
相關服務
相關產品
相關資源
研究small RNA修飾的挑戰與方法 Small RNA修飾的分子機制 small RNA修飾：重要功能與相關疾病研究進展Arraystar small RNA修飾芯片技術服務在單張芯片可定量miRNA，pre-miRNA和tRNA衍生的small RNA（tsRNA，包括tRF＆tiRNA）的堿基修飾?？蓹z測的修飾包括：8-氧代鳥嘌呤（o8G），7-甲基鳥苷（m7G），N6-甲基腺苷（m6A），假尿苷（Ψ）或5-甲基胞苷（m5C）。
芯片優點
? 能夠檢測及定量多種small RNA上修飾：包括o8G，m7G，m6A，Ψ或m5C
? 能夠檢測多種small RNA：包括miRNA，pre-miRNA和tsRNAs（tRF＆tiRNA）
? 金標準準確定量small RNA的修飾: 直接RNA末端標記，避免了測序建庫過程中因修飾導致的cDNA延伸中止的情況，可確保對small RNA修飾定量的高保真性。
? 高靈敏度檢測低水平small RNA的修飾：克服二代測序的局限性，對低表達或低修飾水平的small RNA分析具有出色的分析靈敏度。
? 所需樣品量少，總RNA量可低至1 μg。
Arraystar Small RNA修飾芯片列表
| 服務名稱 | 可檢測的修飾* | 描述 | 規格 |
|---|---|---|---|
| Arraystar Human Small RNA 修飾芯片 | O8G/m7G/m6A/Ψ/m5C | 定量miRNA，pre-miRNA, & tsRNA修飾 | 8 x 15K |
| Arraystar Mouse Small RNA 修飾芯片 | O8G/m7G/m6A/Ψ/m5C | 定量miRNA，pre-miRNA, & tsRNA修飾 | 8 x 15K |
* 單張芯片可從5種修飾中選擇一種進行檢測。
Small RNA修飾高通量篩選面臨的挑戰及解決方案
盡管測序已用于small RNA高通量篩選，但RNA修飾對測序定量的影響仍被嚴重忽視。RNA上多種修飾（m1A，m3C和m1G等）會干擾測序建庫過程中的逆轉錄，因此small RNA-seq對small RNA修飾的定量是不準確的，特別是對small RNA上的修飾。 例如，Small RNA-seq大多偏向檢測18nt的3’tsRNA，而Northern blot主要檢測到的是22nt的同工型3’tsRNA。這是由于TUC存在m1A，會抑制逆轉錄酶進行逆轉錄。大多數small RNA測序數據是從上述文庫構建方法中獲得的，因此，對于有修飾的small RNA，這些數據可能產生誤導。
同樣，small RNA-seq需要多個PCR擴增步驟，這會導致明顯的定量偏差及不準確，因此需要使用獨立正交方法。
事實上，研究修飾的測序方法需要大量的樣本（總RNA> 100 ug），這樣對樣本量有限的研究會產生極大的限制。
此外，small RNA測序通常使用Reads Per Million（RPM）進行標準化，來表示樣品中RNA的相對豐度。 然而，RPM取決于樣品中small RNA的組成。 一個small RNA的RPM的變化將影響所有其它small RNA的值，即使它們的絕對表達水平沒有改變。
因此，就需要克服基于測序方法的局限，開發非測序技術，以更高的靈敏度和準確性來鑒定和定量small RNA的修飾譜。
定量small RNA轉錄后修飾的技術
Arraystar small RNA修飾芯片技術（圖1）將small RNA芯片與RNA免疫沉淀（RIP）進行整合，可在一張芯片上同時檢測修飾及未修飾small RNA水平，為修飾對small RNA（包括miRNA，pre-miRNA和tRF＆tiRNA）的調控提供重要信息，
圖1. Arraystar small RNA修飾芯片技術，分別鑒定和定量small RNA轉錄后修飾，分別為o8G，m7G，m6A，Ψ和m5C。使用特異性抗體通過免疫沉淀富集修飾的small RNA后，使用Arraystar small RNA修飾芯片進行鑒定和定量。
參考文獻
1. Guzzi N et al: Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells. Cell 2018, 173(5):1204-1216 e1226.[PMID: 29628141]
2. Keam SP et al: The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic Acids Res 2014, 42(14):8984-8995.[PMID: 25038252]
3. Keam SP, Sobala A, Ten Have S, Hutvagner G: tRNA-Derived RNA Fragments Associate with Human Multisynthetase Complex (MSC) and Modulate Ribosomal Protein Translation. J Proteome Res 2017, 16(2):413-420.[PMID: 27936807]
4. Zhang X et al: IL-4 Inhibits the Biogenesis of an Epigenetically Suppressive PIWI-Interacting RNA To Upregulate CD1a Molecules on Monocytes/Dendritic Cells. J Immunol 2016, 196(4):1591-1603.[PMID: 26755820]
5. Honda S et al: The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells. Nucleic Acids Res 2017, 45(15):9108-9120.[PMID: 28645172]
6. Cole C et al: Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA 2009, 15(12):2147-2160.[PMID: 19850906]
7. Sobala A, Hutvagner G: Small RNAs derived from the 5' end of tRNA can inhibit protein translation in human cells. RNA Biol 2013, 10(4):553-563.[PMID: 23563448]
8. Lee YS, Shibata Y, Malhotra A, Dutta A: A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 2009, 23(22):2639-2649.[PMID: 19933153]
9. Huang B et al: tRF/miR-1280 Suppresses Stem Cell-like Cells and Metastasis in Colorectal Cancer. Cancer Res 2017, 77(12):3194-3206.[PMID: 28446464]
10. Kuscu C et al: tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 2018, 24(8):1093-1105.[PMID: 29844106]
11. Kim HK et al: A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature 2017, 552(7683):57-62.[PMID: 29186115]
12. Kim HK et al: A tRNA-Derived Small RNA Regulates Ribosomal Protein S28 Protein Levels after Translation Initiation in Humans and Mice. Cell Rep 2019, 29(12):3816-3824 e3814.[PMID: 31851915]
13. Yeung ML et al: Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: evidence for the processing of a viral-cellular double-stranded RNA hybrid. Nucleic Acids Res 2009, 37(19):6575-6586.[PMID: 19729508]
14. Schorn AJ, Gutbrod MJ, LeBlanc C, Martienssen R: LTR-Retrotransposon Control by tRNA-Derived Small RNAs. Cell 2017, 170(1):61-71 e11.[PMID: 28666125]
15. Maute RL et al: tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci U S A 2013, 110(4):1404-1409.[PMID: 23297232]
16. Ruggero K et al: Small noncoding RNAs in cells transformed by human T-cell leukemia virus type 1: a role for a tRNA fragment as a primer for reverse transcriptase. J Virol 2014, 88(7):3612-3622.[PMID: 24403582]
17. Falconi M et al: A novel 3'-tRNA(Glu)-derived fragment acts as a tumor-suppressor in breast cancer by targeting nucleolin. FASEB J 2019:fj201900382RR.[PMID: 31560576]
18. Zhou K et al: A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells. Oncotarget 2017, 8(56):95377-95391.[PMID: 29221134]
19. Goodarzi H et al: Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell 2015, 161(4):790-802.[PMID: 25957686]
20. Natt D et al: Human sperm displays rapid responses to diet. PLoS Biol 2019, 17(12):e3000559.[PMID: 31877125]
21. Veneziano D et al: Dysregulation of different classes of tRNA fragments in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2019, 116(48):24252-24258.[PMID: 31723042]
22. Haussecker D et al: Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA 2010, 16(4):673-695.[PMID: 20181738]
23. Balatti V et al: tsRNA signatures in cancer. Proc Natl Acad Sci U S A 2017, 114(30):8071-8076.[PMID: 28696308]
24. Cho H et al: Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments. Nucleic Acids Res 2019, 47(18):9888-9901.[PMID: 31504775]
25. Babiarz JE et al: Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 2008, 22(20):2773-2785.[PMID: 18923076]
26. Hasler D et al: The Lupus Autoantigen La Prevents Mis-channeling of tRNA Fragments into the Human MicroRNA Pathway. Mol Cell 2016, 63(1):110-124.[PMID: 27345152]
27. Pekarsky Y et al: Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer. Proc Natl Acad Sci U S A 2016, 113(18):5071-5076.[PMID: 27071132]
28. Liao JY et al: Deep sequencing of human nuclear and cytoplasmic small RNAs reveals an unexpectedly complex subcellular distribution of miRNAs and tRNA 3' trailers. PLoS One 2010, 5(5):e10563.[PMID: 20498841]
29. La Ferlita A et al: Identification of tRNA-derived ncRNAs in TCGA and NCI-60 panel cell lines and development of the public database tRFexplorer. Database (Oxford) 2019, 2019.[PMID: 31735953]
30. Honda S et al: Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. Proc Natl Acad Sci U S A 2015, 112(29):E3816-3825.[PMID: 26124144]
31. Donovan J, Rath S, Kolet-Mandrikov D, Korennykh A: Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery. RNA 2017, 23(11):1660-1671.[PMID: 28808124]
32. Hanada T et al: CLP1 links tRNA metabolism to progressive motor-neuron loss. Nature 2013, 495(7442):474-480.[PMID: 23474986]
33. Saikia M et al: Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress. Mol Cell Biol 2014, 34(13):2450-2463.[PMID: 24752898]
34. Wang Q et al: Identification and functional characterization of tRNA-derived RNA fragments (tRFs) in respiratory syncytial virus infection. Mol Ther 2013, 21(2):368-379.[PMID: 23183536]
35. Deng J et al: Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism. Mol Ther 2015, 23(10):1622-1629.[PMID: 26156244]
36. Zhou J et al: Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection. J Gen Virol 2017, 98(7):1600-1610.[PMID: 28708049]
37. Yang X et al: 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m(5)C reader. Cell Res 2017, 27(5):606-625.[PMID: 28418038]
38. Ivanov P et al: Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell 2011, 43(4):613-623.[PMID: 21855800]
39. Ivanov P et al: G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments. Proc Natl Acad Sci U S A 2014, 111(51):18201-18206.[PMID: 25404306]
40. Schaffer AE et al: CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell 2014, 157(3):651-663.[PMID: 24766810]
Arraystar Human small RNA 修飾芯片 V1.0
| 探針總數 | 14,706 |
|---|---|
| 探針設計策略 | 整個探針由5’cap區， small RNA特異性區和3’linker區組成。 |
| 探針結合位點 |
5-p-miRNA 和 5'tsRNA: small RNA的3’區域 3-p-miRNA 和 3'tsRNA: small RNA的5’區域 Pre-miRNA: pre-miRNA的頸環區域設計 |
| 探針特異性 | small RNA特異性 |
| miRNA數目 | 2,628 (1,319個5-p-miRNAs, 1,309個3-p-miRNAs) |
| pre-miRNAs數目 | 1,745 |
| tsRNAs數目 | 5,128 |
| Small RNA來源數據庫 |
miRNA: miRBase (v22) pre-miRNA: miRBase (v22) tsRNA: tRFdb, GtRNADb (更新至18.1 2019.08) 文獻: 公開發表的文獻至 2019 [1-40] |
| 芯片規格 | 8 x 15K |
Arraystar Mouse small RNA 修飾芯片 V1.0
| 探針總數 | 14,895 |
|---|---|
| 探針設計策略 | 整個探針由5’cap區， small RNA特異性區和3’linker區組成。 |
| 探針結合位點 |
5-p-miRNA 和 5'tsRNA: small RNA的3’區域 3-p-miRNA 和 3'tsRNA: small RNA的5’區域 Pre-miRNA: pre-miRNA的頸環區域設計 |
| 探針特異性 | small RNA特異性 |
| miRNA數目 | 1949 (966個5-p-miRNAs, 983個3-p-miRNAs) |
| pre-miRNAs數目 | 1,122 |
| tsRNAs數目 | 1,809 |
| Small RNA來源數據庫 |
miRNA: miRBase (v22) pre-miRNA: miRBase (v22) tsRNA: tRFdb, GtRNADb (更新至18.1 2019.08) 文獻: 公開發表的文獻至 2019 [1-40] |
| 芯片規格 | 8 x 15K |
References
1. Guzzi N et al: Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells. Cell 2018, 173(5):1204-1216 e1226.[PMID: 29628141]
2. Keam SP et al: The human Piwi protein Hiwi2 associates with tRNA-derived piRNAs in somatic cells. Nucleic Acids Res 2014, 42(14):8984-8995.[PMID: 25038252]
3. Keam SP, Sobala A, Ten Have S, Hutvagner G: tRNA-Derived RNA Fragments Associate with Human Multisynthetase Complex (MSC) and Modulate Ribosomal Protein Translation. J Proteome Res 2017, 16(2):413-420.[PMID: 27936807]
4. Zhang X et al: IL-4 Inhibits the Biogenesis of an Epigenetically Suppressive PIWI-Interacting RNA To Upregulate CD1a Molecules on Monocytes/Dendritic Cells. J Immunol 2016, 196(4):1591-1603.[PMID: 26755820]
5. Honda S et al: The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells. Nucleic Acids Res 2017, 45(15):9108-9120.[PMID: 28645172]
6. Cole C et al: Filtering of deep sequencing data reveals the existence of abundant Dicer-dependent small RNAs derived from tRNAs. RNA 2009, 15(12):2147-2160.[PMID: 19850906]
7. Sobala A, Hutvagner G: Small RNAs derived from the 5' end of tRNA can inhibit protein translation in human cells. RNA Biol 2013, 10(4):553-563.[PMID: 23563448]
8. Lee YS, Shibata Y, Malhotra A, Dutta A: A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev 2009, 23(22):2639-2649.[PMID: 19933153]
9. Huang B et al: tRF/miR-1280 Suppresses Stem Cell-like Cells and Metastasis in Colorectal Cancer. Cancer Res 2017, 77(12):3194-3206.[PMID: 28446464]
10. Kuscu C et al: tRNA fragments (tRFs) guide Ago to regulate gene expression post-transcriptionally in a Dicer-independent manner. RNA 2018, 24(8):1093-1105.[PMID: 29844106]
11. Kim HK et al: A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature 2017, 552(7683):57-62.[PMID: 29186115]
12. Kim HK et al: A tRNA-Derived Small RNA Regulates Ribosomal Protein S28 Protein Levels after Translation Initiation in Humans and Mice. Cell Rep 2019, 29(12):3816-3824 e3814.[PMID: 31851915]
13. Yeung ML et al: Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: evidence for the processing of a viral-cellular double-stranded RNA hybrid. Nucleic Acids Res 2009, 37(19):6575-6586.[PMID: 19729508]
14. Schorn AJ, Gutbrod MJ, LeBlanc C, Martienssen R: LTR-Retrotransposon Control by tRNA-Derived Small RNAs. Cell 2017, 170(1):61-71 e11.[PMID: 28666125]
15. Maute RL et al: tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci U S A 2013, 110(4):1404-1409.[PMID: 23297232]
16. Ruggero K et al: Small noncoding RNAs in cells transformed by human T-cell leukemia virus type 1: a role for a tRNA fragment as a primer for reverse transcriptase. J Virol 2014, 88(7):3612-3622.[PMID: 24403582]
17. Falconi M et al: A novel 3'-tRNA(Glu)-derived fragment acts as a tumor-suppressor in breast cancer by targeting nucleolin. FASEB J 2019:fj201900382RR.[PMID: 31560576]
18. Zhou K et al: A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells. Oncotarget 2017, 8(56):95377-95391.[PMID: 29221134]
19. Goodarzi H et al: Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell 2015, 161(4):790-802.[PMID: 25957686]
20. Natt D et al: Human sperm displays rapid responses to diet. PLoS Biol 2019, 17(12):e3000559.[PMID: 31877125]
21. Veneziano D et al: Dysregulation of different classes of tRNA fragments in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 2019, 116(48):24252-24258.[PMID: 31723042]
22. Haussecker D et al: Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA 2010, 16(4):673-695.[PMID: 20181738]
23. Balatti V et al: tsRNA signatures in cancer. Proc Natl Acad Sci U S A 2017, 114(30):8071-8076.[PMID: 28696308]
24. Cho H et al: Regulation of La/SSB-dependent viral gene expression by pre-tRNA 3' trailer-derived tRNA fragments. Nucleic Acids Res 2019, 47(18):9888-9901.[PMID: 31504775]
25. Babiarz JE et al: Mouse ES cells express endogenous shRNAs, siRNAs, and other Microprocessor-independent, Dicer-dependent small RNAs. Genes Dev 2008, 22(20):2773-2785.[PMID: 18923076]
26. Hasler D et al: The Lupus Autoantigen La Prevents Mis-channeling of tRNA Fragments into the Human MicroRNA Pathway. Mol Cell 2016, 63(1):110-124.[PMID: 27345152]
27. Pekarsky Y et al: Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer. Proc Natl Acad Sci U S A 2016, 113(18):5071-5076.[PMID: 27071132]
28. Liao JY et al: Deep sequencing of human nuclear and cytoplasmic small RNAs reveals an unexpectedly complex subcellular distribution of miRNAs and tRNA 3' trailers. PLoS One 2010, 5(5):e10563.[PMID: 20498841]
29. La Ferlita A et al: Identification of tRNA-derived ncRNAs in TCGA and NCI-60 panel cell lines and development of the public database tRFexplorer. Database (Oxford) 2019, 2019.[PMID: 31735953]
30. Honda S et al: Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. Proc Natl Acad Sci U S A 2015, 112(29):E3816-3825.[PMID: 26124144]
31. Donovan J, Rath S, Kolet-Mandrikov D, Korennykh A: Rapid RNase L-driven arrest of protein synthesis in the dsRNA response without degradation of translation machinery. RNA 2017, 23(11):1660-1671.[PMID: 28808124]
32. Hanada T et al: CLP1 links tRNA metabolism to progressive motor-neuron loss. Nature 2013, 495(7442):474-480.[PMID: 23474986]
33. Saikia M et al: Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress. Mol Cell Biol 2014, 34(13):2450-2463.[PMID: 24752898]
34. Wang Q et al: Identification and functional characterization of tRNA-derived RNA fragments (tRFs) in respiratory syncytial virus infection. Mol Ther 2013, 21(2):368-379.[PMID: 23183536]
35. Deng J et al: Respiratory Syncytial Virus Utilizes a tRNA Fragment to Suppress Antiviral Responses Through a Novel Targeting Mechanism. Mol Ther 2015, 23(10):1622-1629.[PMID: 26156244]
36. Zhou J et al: Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection. J Gen Virol 2017, 98(7):1600-1610.[PMID: 28708049]
37. Yang X et al: 5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m(5)C reader. Cell Res 2017, 27(5):606-625.[PMID: 28418038]
38. Ivanov P et al: Angiogenin-induced tRNA fragments inhibit translation initiation. Mol Cell 2011, 43(4):613-623.[PMID: 21855800]
39. Ivanov P et al: G-quadruplex structures contribute to the neuroprotective effects of angiogenin-induced tRNA fragments. Proc Natl Acad Sci U S A 2014, 111(51):18201-18206.[PMID: 25404306]
40. Schaffer AE et al: CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell 2014, 157(3):651-663.[PMID: 24766810]
數據分析包括可直接使用的關鍵數據、豐富的注釋信息和出版級別的圖形。
差異修飾small RNA列表，包括miRNA，pre-miRNA和tsRNA（tRF＆tiRNA）
MatureID: 成熟miRNA在miRBase 的ID
Group m7G miRNA level (normalized, log2): 基于Cy5標記的m7G-IP RNA的初始信號值得到的log2轉換的標準化后的組平均值。
Treated, Control: 實驗組和對照組
FC: 兩組比較的差異倍數
P: t test檢驗分析的統計學差異的p值
Regulation: 兩組比較的上調或者下調
Group m7G %modified miRNA: m7G修飾的miRNA組平均百分比
miRNA_family: 具有相同的種子序列的miRNA家族
m7G_motif: “RAm7GGT” m7G 的motif基序, R 代表G或A
差異修飾的miRNA，pre-miRNA和tsRNA（tRF＆tiRNA）的分層聚類熱圖
圖1.差異修飾small RNA的分層聚類熱圖。 修飾的RNA水平由左上方小圖中紅藍色色標表示。頂部樹狀圖顯示了樣品之間修飾圖譜相對接近度。組別由熱圖上方的色條表示。
