Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT3KYJQL)

• DOT Name: Fibrillin-2 (FBN2)
• Gene Name: FBN2
• Related Disease:
  Arthrogryposis, distal, type 1A
  Arthrogryposis, distal, type 1B
  Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome
  Colon cancer
  Colon carcinoma
  Congenital contractural arachnodactyly
  Distal arthrogryposis type 5D
  Freeman-Sheldon syndrome
  Gordon syndrome
  Sheldon-hall syndrome
  Trismus-pseudocamptodactyly syndrome
  Adenocarcinoma
  Advanced cancer
  Androgen insensitivity syndrome
  Arteriosclerosis
  Arthrogryposis
  Atherosclerosis
  Cardiovascular disease
  Cholangiocarcinoma
  Clear cell renal carcinoma
  Colorectal carcinoma
  Connective tissue disorder
  Distal arthrogryposis
  Hepatocellular carcinoma
  Hereditary disorder of connective tissue
  Marfan syndrome
  Migraine disorder
  Neoplasm
  Non-insulin dependent diabetes
  Primary sclerosing cholangitis
  Age-related macular degeneration
  Carcinoma
  Hepatobiliary disorder
  Type-1/2 diabetes
  Colorectal neoplasm
  Lung cancer
  Lung carcinoma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Carpal tunnel syndrome
  Coronary heart disease
  Familial thoracic aortic aneurysm and aortic dissection
  Hepatitis C virus infection
  Macular degeneration, early-onset
  Pancreatic cancer
• UniProt ID: FBN2_HUMAN
• Pfam ID: PF12662 ; PF12947 ; PF07645 ; PF21364 ; PF18193 ; PF14670 ; PF12661 ; PF00683
• Sequence:
  MGRRRRLCLQLYFLWLGCVVLWAQGTAGQPQPPPPKPPRPQPPPQQVRSATAGSEGGFLA
  PEYREEGAAVASRVRRRGQQDVLRGPNVCGSRFHSYCCPGWKTLPGGNQCIVPICRNSCG
  DGFCSRPNMCTCSSGQISSTCGSKSIQQCSVRCMNGGTCADDHCQCQKGYIGTYCGQPVC
  ENGCQNGGRCIGPNRCACVYGFTGPQCERDYRTGPCFTQVNNQMCQGQLTGIVCTKTLCC
  ATIGRAWGHPCEMCPAQPQPCRRGFIPNIRTGACQDVDECQAIPGICQGGNCINTVGSFE
  CRCPAGHKQSETTQKCEDIDECSIIPGICETGECSNTVGSYFCVCPRGYVTSTDGSRCID
  QRTGMCFSGLVNGRCAQELPGRMTKMQCCCEPGRCWGIGTIPEACPVRGSEEYRRLCMDG
  LPMGGIPGSAGSRPGGTGGNGFAPSGNGNGYGPGGTGFIPIPGGNGFSPGVGGAGVGAGG
  QGPIITGLTILNQTIDICKHHANLCLNGRCIPTVSSYRCECNMGYKQDANGDCIDVDECT
  SNPCTNGDCVNTPGSYYCKCHAGFQRTPTKQACIDIDECIQNGVLCKNGRCVNTDGSFQC
  ICNAGFELTTDGKNCVDHDECTTTNMCLNGMCINEDGSFKCICKPGFVLAPNGRYCTDVD
  ECQTPGICMNGHCINSEGSFRCDCPPGLAVGMDGRVCVDTHMRSTCYGGIKKGVCVRPFP
  GAVTKSECCCANPDYGFGEPCQPCPAKNSAEFHGLCSSGVGITVDGRDINECALDPDICA
  NGICENLRGSYRCNCNSGYEPDASGRNCIDIDECLVNRLLCDNGLCRNTPGSYSCTCPPG
  YVFRTETETCEDINECESNPCVNGACRNNLGSFNCECSPGSKLSSTGLICIDSLKGTCWL
  NIQDSRCEVNINGATLKSECCATLGAAWGSPCERCELDTACPRGLARIKGVTCEDVNECE
  VFPGVCPNGRCVNSKGSFHCECPEGLTLDGTGRVCLDIRMEQCYLKWDEDECIHPVPGKF
  RMDACCCAVGAAWGTECEECPKPGTKEYETLCPRGAGFANRGDVLTGRPFYKDINECKAF
  PGMCTYGKCRNTIGSFKCRCNSGFALDMEERNCTDIDECRISPDLCGSGICVNTPGSFEC
  ECFEGYESGFMMMKNCMDIDECERNPLLCRGGTCVNTEGSFQCDCPLGHELSPSREDCVD
  INECSLSDNLCRNGKCVNMIGTYQCSCNPGYQATPDRQGCTDIDECMIMNGGCDTQCTNS
  EGSYECSCSEGYALMPDGRSCADIDECENNPDICDGGQCTNIPGEYRCLCYDGFMASMDM
  KTCIDVNECDLNSNICMFGECENTKGSFICHCQLGYSVKKGTTGCTDVDECEIGAHNCDM
  HASCLNIPGSFKCSCREGWIGNGIKCIDLDECSNGTHQCSINAQCVNTPGSYRCACSEGF
  TGDGFTCSDVDECAENINLCENGQCLNVPGAYRCECEMGFTPASDSRSCQDIDECSFQNI
  CVFGTCNNLPGMFHCICDDGYELDRTGGNCTDIDECADPINCVNGLCVNTPGRYECNCPP
  DFQLNPTGVGCVDNRVGNCYLKFGPRGDGSLSCNTEIGVGVSRSSCCCSLGKAWGNPCET
  CPPVNSTEYYTLCPGGEGFRPNPITIILEDIDECQELPGLCQGGNCINTFGSFQCECPQG
  YYLSEDTRICEDIDECFAHPGVCGPGTCYNTLGNYTCICPPEYMQVNGGHNCMDMRKSFC
  YRSYNGTTCENELPFNVTKRMCCCTYNVGKAWNKPCEPCPTPGTADFKTICGNIPGFTFD
  IHTGKAVDIDECKEIPGICANGVCINQIGSFRCECPTGFSYNDLLLVCEDIDECSNGDNL
  CQRNADCINSPGSYRCECAAGFKLSPNGACVDRNECLEIPNVCSHGLCVDLQGSYQCICH
  NGFKASQDQTMCMDVDECERHPCGNGTCKNTVGSYNCLCYPGFELTHNNDCLDIDECSSF
  FGQVCRNGRCFNEIGSFKCLCNEGYELTPDGKNCIDTNECVALPGSCSPGTCQNLEGSFR
  CICPPGYEVKSENCIDINECDEDPNICLFGSCTNTPGGFQCLCPPGFVLSDNGRRCFDTR
  QSFCFTNFENGKCSVPKAFNTTKAKCCCSKMPGEGWGDPCELCPKDDEVAFQDLCPYGHG
  TVPSLHDTREDVNECLESPGICSNGQCINTDGSFRCECPMGYNLDYTGVRCVDTDECSIG
  NPCGNGTCTNVIGSFECNCNEGFEPGPMMNCEDINECAQNPLLCAFRCMNTFGSYECTCP
  IGYALREDQKMCKDLDECAEGLHDCESRGMMCKNLIGTFMCICPPGMARRPDGEGCVDEN
  ECRTKPGICENGRCVNIIGSYRCECNEGFQSSSSGTECLDNRQGLCFAEVLQTICQMASS
  SRNLVTKSECCCDGGRGWGHQCELCPLPGTAQYKKICPHGPGYTTDGRDIDECKVMPNLC
  TNGQCINTMGSFRCFCKVGYTTDISGTSCIDLDECSQSPKPCNYICKNTEGSYQCSCPRG
  YVLQEDGKTCKDLDECQTKQHNCQFLCVNTLGGFTCKCPPGFTQHHTACIDNNECGSQPS
  LCGAKGICQNTPGSFSCECQRGFSLDATGLNCEDVDECDGNHRCQHGCQNILGGYRCGCP
  QGYIQHYQWNQCVDENECSNPNACGSASCYNTLGSYKCACPSGFSFDQFSSACHDVNECS
  SSKNPCNYGCSNTEGGYLCGCPPGYYRVGQGHCVSGMGFNKGQYLSLDTEVDEENALSPE
  ACYECKINGYSKKDSRQKRSIHEPDPTAVEQISLESVDMDSPVNMKFNLSHLGSKEHILE
  LRPAIQPLNNHIRYVISQGNDDSVFRIHQRNGLSYLHTAKKKLMPGTYTLEITSIPLYKK
  KELKKLEESNEDDYLLGELGEALRMRLQIQLY
• Function: [Fibrillin-2]: Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles. Fibrillin-2-containing microfibrils regulate the early process of elastic fiber assembly. Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively; [Placensin]: Hormone secreted by trophoblasts that promotes trophoblast invasiveness. Has glucogenic activity: is able to increase plasma glucose levels.
• Tissue Specificity: Almost exclusively expressed in placenta . Expressed at much lower level in other tissues . Expressed in fetal eye (18 weeks)in the retinal pigment epithelium (RPE), the choroid, Bruch's membrane and in the sclera . Not expressed in the neural retina .; [Placensin]: Present at high level in cytotrophoblasts as compared with syncytiotrophoblasts at 8-9 weeks of pregnancy (at protein level) . Levels in the serum increase during pregnancy (at protein level) .
• KEGG Pathway: Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  Elastic fibre formation (R-HSA-1566948)
  Molecules associated with elastic fibres (R-HSA-2129379)
  Degradation of the extracellular matrix (R-HSA-1474228)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthrogryposis, distal, type 1A	DISD8IKM	Definitive	Biomarker	[1]
Arthrogryposis, distal, type 1B	DISHXTV4	Definitive	Biomarker	[1]
Arthrogryposis- oculomotor limitation-electroretinal anomalies syndrome	DISBCS1Y	Definitive	Biomarker	[1]
Colon cancer	DISVC52G	Definitive	Biomarker	[2]
Colon carcinoma	DISJYKUO	Definitive	Biomarker	[2]
Congenital contractural arachnodactyly	DISOM1K7	Definitive	Autosomal dominant	[3]
Distal arthrogryposis type 5D	DISYDVKR	Definitive	Biomarker	[1]
Freeman-Sheldon syndrome	DIS7V9PS	Definitive	Biomarker	[1]
Gordon syndrome	DISVMP0Y	Definitive	Biomarker	[1]
Sheldon-hall syndrome	DISOCVMC	Definitive	Biomarker	[1]
Trismus-pseudocamptodactyly syndrome	DISZ2Y71	Definitive	Biomarker	[1]
Adenocarcinoma	DIS3IHTY	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
Androgen insensitivity syndrome	DISUZBBO	Strong	Altered Expression	[6]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[7]
Arthrogryposis	DISC81CM	Strong	Genetic Variation	[8]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[7]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[9]
Cholangiocarcinoma	DIS71F6X	Strong	Genetic Variation	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Connective tissue disorder	DISKXBS3	Strong	Genetic Variation	[12]
Distal arthrogryposis	DIS3QIEL	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
Hereditary disorder of connective tissue	DIS8I9FS	Strong	Genetic Variation	[14]
Marfan syndrome	DISVEUWZ	Strong	Genetic Variation	[15]
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[16]
Neoplasm	DISZKGEW	Strong	Biomarker	[17]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[9]
Primary sclerosing cholangitis	DISTH5WJ	Strong	Biomarker	[18]
Age-related macular degeneration	DIS0XS2C	moderate	Genetic Variation	[19]
Carcinoma	DISH9F1N	moderate	Altered Expression	[20]
Hepatobiliary disorder	DISEW817	moderate	Biomarker	[5]
Type-1/2 diabetes	DISIUHAP	moderate	Genetic Variation	[21]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[22]
Lung cancer	DISCM4YA	Disputed	Posttranslational Modification	[23]
Lung carcinoma	DISTR26C	Disputed	Posttranslational Modification	[23]
Metastatic malignant neoplasm	DIS86UK6	Disputed	Biomarker	[24]
Non-small-cell lung cancer	DIS5Y6R9	Disputed	Posttranslational Modification	[23]
Carpal tunnel syndrome	DISHQ3BE	Limited	Autosomal dominant	[25]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[26]
Familial thoracic aortic aneurysm and aortic dissection	DIS069FB	Limited	Autosomal dominant	[27]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[28]
Macular degeneration, early-onset	DISLVC95	Limited	Autosomal dominant	[29]
Pancreatic cancer	DISJC981	Limited	Biomarker	[30]

23 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Fibrillin-2 (FBN2).	[31]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fibrillin-2 (FBN2).	[32]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fibrillin-2 (FBN2).	[33]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Fibrillin-2 (FBN2).	[34]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Fibrillin-2 (FBN2).	[35]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Fibrillin-2 (FBN2).	[36]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Fibrillin-2 (FBN2).	[37]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Fibrillin-2 (FBN2).	[38]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Fibrillin-2 (FBN2).	[39]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Fibrillin-2 (FBN2).	[40]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Fibrillin-2 (FBN2).	[41]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Fibrillin-2 (FBN2).	[32]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Fibrillin-2 (FBN2).	[42]
Guaiacol	DMN4E7T	Phase 3	Guaiacol decreases the expression of Fibrillin-2 (FBN2).	[42]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Fibrillin-2 (FBN2).	[42]
Puerarin	DMJIMXH	Phase 2	Puerarin decreases the expression of Fibrillin-2 (FBN2).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Fibrillin-2 (FBN2).	[43]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Fibrillin-2 (FBN2).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Fibrillin-2 (FBN2).	[47]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Fibrillin-2 (FBN2).	[48]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Fibrillin-2 (FBN2).	[49]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Fibrillin-2 (FBN2).	[50]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the expression of Fibrillin-2 (FBN2).	[42]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Fibrillin-2 (FBN2).	[44]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Fibrillin-2 (FBN2).	[46]

References

• [1] ENU mutagenesis reveals a novel phenotype of reduced limb strength in mice lacking fibrillin 2.PLoS One. 2010 Feb 9;5(2):e9137. doi: 10.1371/journal.pone.0009137.
• [2] DNA methylation biomarker candidates for early detection of colon cancer.Tumour Biol. 2012 Apr;33(2):363-72. doi: 10.1007/s13277-011-0302-2. Epub 2012 Jan 12.
• [3] Two novel fibrillin-2 mutations in congenital contractural arachnodactyly. Am J Med Genet. 2000 May 1;92(1):7-12.
• [4] Clinicopathological and molecular characteristics of synchronous gastric adenocarcinoma and gastrointestinal stromal tumors.Sci Rep. 2017 Oct 10;7(1):12890. doi: 10.1038/s41598-017-12622-x.
• [5] Opisthorchis viverrini Draft Genome - Biomedical Implications and Future Avenues.Adv Parasitol. 2018;101:125-148. doi: 10.1016/bs.apar.2018.05.005. Epub 2018 Jun 6.
• [6] New Evidence Supporting the Role of FBN1 in the Development of Adolescent Idiopathic Scoliosis.Spine (Phila Pa 1976). 2019 Feb 15;44(4):E225-E232. doi: 10.1097/BRS.0000000000002809.
• [7] Healthy Lifestyle During the Midlife Is Prospectively Associated With Less Subclinical Carotid Atherosclerosis: The Study of Women's Health Across the Nation.J Am Heart Assoc. 2018 Dec 4;7(23):e010405. doi: 10.1161/JAHA.118.010405.
• [8] Exome sequencing reveals blended phenotype of double heterozygous FBN1 and FBN2 variants in a fetus.Eur J Med Genet. 2018 Jul;61(7):399-402. doi: 10.1016/j.ejmg.2018.02.009. Epub 2018 Mar 1.
• [9] Type 2 diabetes associated variants of KCNQ1 strongly confer the risk of cardiovascular disease among the Saudi Arabian population.Genet Mol Biol. 2017 Jul-Sep;40(3):586-590. doi: 10.1590/1678-4685-GMB-2017-0005. Epub 2017 Aug 31.
• [10] Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study.J Crohns Colitis. 2019 Dec 10;13(12):1492-1500. doi: 10.1093/ecco-jcc/jjz094.
• [11] Tumor-specific hypermethylation of epigenetic biomarkers, including SFRP1, predicts for poorer survival in patients from the TCGA Kidney Renal Clear Cell Carcinoma (KIRC) project.PLoS One. 2014 Jan 15;9(1):e85621. doi: 10.1371/journal.pone.0085621. eCollection 2014.
• [12] Establishment of a Beals syndrome patient-derived human induced pluripotent stem cell line HELPi001-A.Stem Cell Res. 2019 Oct;40:101535. doi: 10.1016/j.scr.2019.101535. Epub 2019 Aug 8.
• [13] Radiological features and outcomes ofcombined hepatocellular-cholangiocarcinoma inpatients undergoingsurgical resection.J Formos Med Assoc. 2020 Jan;119(1 Pt 1):125-133. doi: 10.1016/j.jfma.2019.02.012. Epub 2019 Mar 12.
• [14] Prenatal diagnosis in congenital contractural arachnodactyly.Genet Test. 1997-1998;1(4):293-6. doi: 10.1089/gte.1997.1.293.
• [15] Variant filtering, digenic variants, and other challenges in clinical sequencing: a lesson from fibrillinopathies.Clin Genet. 2020 Feb;97(2):235-245. doi: 10.1111/cge.13640. Epub 2019 Oct 1.
• [16] Genome-wide meta-analysis identifies new susceptibility loci for migraine.Nat Genet. 2013 Aug;45(8):912-917. doi: 10.1038/ng.2676. Epub 2013 Jun 23.
• [17] Combining imaging and tumour biopsy improves the diagnosis of combined hepatocellular-cholangiocarcinoma.Liver Int. 2019 Dec;39(12):2386-2396. doi: 10.1111/liv.14261. Epub 2019 Oct 20.
• [18] Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis.Hepatology. 2019 Aug;70(2):547-562. doi: 10.1002/hep.30319. Epub 2019 Feb 14.
• [19] Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration. Hum Mol Genet. 2014 Nov 1;23(21):5827-37. doi: 10.1093/hmg/ddu276. Epub 2014 Jun 4.
• [20] The correlation between poor prognosis and increased yes-associated protein 1 expression in keratin 19 expressing hepatocellular carcinomas and cholangiocarcinomas.BMC Cancer. 2017 Jun 23;17(1):441. doi: 10.1186/s12885-017-3431-1.
• [21] The carriage of risk variants of CDKAL1 impairs beta-cell function in both diabetic and non-diabetic patients and reduces response to non-sulfonylurea and sulfonylurea agonists of the pancreatic KATP channel.Acta Diabetol. 2011 Sep;48(3):227-35. doi: 10.1007/s00592-011-0299-4. Epub 2011 May 25.
• [22] Genomic and epigenomic integration identifies a prognostic signature in colon cancer.Clin Cancer Res. 2011 Mar 15;17(6):1535-45. doi: 10.1158/1078-0432.CCR-10-2509. Epub 2011 Jan 28.
• [23] Aberrant methylation of FBN2 in human non-small cell lung cancer.Lung Cancer. 2005 Oct;50(1):43-9. doi: 10.1016/j.lungcan.2005.04.013.
• [24] Up-regulated LINC00261 predicts a poor prognosis and promotes a metastasis by EMT process in cholangiocarcinoma.Pathol Res Pract. 2020 Jan;216(1):152733. doi: 10.1016/j.prp.2019.152733. Epub 2019 Nov 11.
• [25] Delineation of a new fibrillin-2-opathy with evidence for a role of FBN2 in the pathogenesis of carpal tunnel syndrome. J Med Genet. 2021 Nov;58(11):778-782. doi: 10.1136/jmedgenet-2020-107085. Epub 2020 Sep 8.
• [26] A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes.Anatol J Cardiol. 2015 Oct;15(10):823-9. doi: 10.5152/akd.2014.5762. Epub 2014 Oct 31.
• [27] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [28] Single nucleotide polymorphisms of toll-like receptor 7 in hepatitis C virus infection patients from a high-risk chinese population.Inflammation. 2015 Feb;38(1):142-51. doi: 10.1007/s10753-014-0016-x.
• [29] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [30] Discovery of glycocholic acid and taurochenodeoxycholic acid as phenotypic biomarkers in cholangiocarcinoma.Sci Rep. 2018 Jul 23;8(1):11088. doi: 10.1038/s41598-018-29445-z.
• [31] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [32] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [33] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [34] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [35] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [36] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [37] Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A. 2005 May 24;102(21):7653-8.
• [38] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [39] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [40] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [41] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [42] Examining the genomic influence of skin antioxidants in vitro. Mediators Inflamm. 2010;2010.
• [43] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [44] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [45] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [46] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [47] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [48] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [49] Linking site-specific loss of histone acetylation to repression of gene expression by the mycotoxin ochratoxin A. Arch Toxicol. 2018 Feb;92(2):995-1014.
• [50] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.