Abstract
Multiple myeloma (MM) is a common type of blood cancer affecting plasma cells originating from the lymphoid B-cell lineage. It accounts for about 10% of all hematological malignancies and can cause significant end-organ damage. The emergence of genomic technologies such as next-generation sequencing and gene expression analysis has opened new possibilities for early detection of multiple myeloma and identification of personalized treatment options. However, there remain significant challenges to overcome in MM research, including integrating multi-omics data, achieving a comprehensive understanding of the disease, and developing targeted therapies and biomarkers. The extensive data generated by these technologies presents another challenge for data analysis and interpretation. To bridge this gap, we have developed a multi-omics open-access database called MyeloDB. It includes gene expression profiling, high-throughput CRISPR-Cas9 screens, drug sensitivity resources profile, and biomarkers. MyeloDB contains 47 expression profiles, 3 methylation profiles comprising a total of 5630 patient samples and 25 biomarkers which were reported in previous studies. In addition to this, MyeloDB can provide significant insight of gene mutations in MM on drug sensitivity. Furthermore, users can download the datasets and conduct their own analyses. Utilizing this database, we have identified five novel genes, i.e., CBFB, MANF, MBNL1, SEPHS2, and UFM1 as potential drug targets for MM. We hope MyeloDB will serve as a comprehensive platform for researchers and foster novel discoveries in MM. MyeloDB Database URL: https://project.iith.ac.in/cgntlab/myelodb/.
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Data Availability
The datasets used in this study are available on MyeloDB database website (https://project.iith.ac.in/cgntlab/myelodb).
Abbreviations
- MM:
-
Multiple myeloma
- MGUS:
-
Monoclonal gammopathy of undetermined significance
- SMM:
-
Smoldering multiple myeloma
- GDC:
-
Genomic Data Commons
- GDSC:
-
Genomics of Drug Sensitivity in Cancer
- ICGC:
-
International Cancer Genome Consortium
- DepMap:
-
Dependency map
- TCGA:
-
The Cancer Genome Atlas
- GEO:
-
Gene Expression Omnibus
- IMWG:
-
International Myeloma Working Group
- COSMIC:
-
Catalogue of Somatic Mutations in Cancer
- CMD:
-
Complete mutation data
- RMA:
-
Robust Multichip Average
- TPM:
-
Transcripts per million
- RPKM:
-
Reads per kilobase per million mapped
- FPKM:
-
Fragments per kilobase of transcript per million
- CGC:
-
Cancer Gene Census
References
Alvarez-Benayas J, Trasanidis N, Katsarou A, Ponnusamy K, Chaidos A, May PC, Xiao X, Bua M, Atta M, Roberts IAG, Auner HW, Hatjiharissi E, Papaioannou M, Caputo VS, Sudbery IM, Karadimitris A (2021) Chromatin-based, in cis and in trans regulatory rewiring underpins distinct oncogenic transcriptomes in multiple myeloma. Nat Commun 12(1):1–16. https://doi.org/10.1038/s41467-021-25704-2
Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A (2013) NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res 41. https://doi.org/10.1093/NAR/GKS1193. (Database issue)
Blade J, Kyle RA, Greipp PR (1996) Multiple myeloma in patients younger than 30 years. Report of 10 cases and review of the literature. Arch Intern Med 156(13):1463. https://doi.org/10.1001/ARCHINTE.1996.00440120125014
Carvajal-Vergara X, Tabera S, Montero JC, Esparís-Ogando A, López-Pérez R, Mateo G, Gutiérrez N, Parmo-Cabañas M, Teixidó J, San Miguel JF, Pandiella A (2005) Multifunctional role of Erk5 in multiple myeloma. Blood 105(11):4492–4499. https://doi.org/10.1182/BLOOD-2004-08-2985
Carvalho BS, Irizarry RA (2010) A framework for oligonucleotide microarray preprocessing. Bioinformatics (oxford, England) 26(19):2363–2367. https://doi.org/10.1093/BIOINFORMATICS/BTQ431
Cowan AJ, Green DJ, Kwok M, Lee S, Coffey DG, Holmberg LA, Tuazon S, Gopal AK, Libby EN (2022) Diagnosis and management of multiple myeloma: a review. JAMA 327(5):464–477. https://doi.org/10.1001/JAMA.2022.0003
Davies FE, Dring AM, Li C, Rawstron AC, Shammas M A, O’Connor SM, Fenton JAL, Hideshima T, Chauhan D, Tai IT, Robinson E, Auclair D, Rees K, Gonzalez D, Ashcroft AJ, Dasgupta R, Mitsiades C, Mitsiades N, Chen LB, … Anderson KC (2003) Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood 102(13):4504–4511. https://doi.org/10.1182/BLOOD-2003-01-0016
DepMap, Broad (2022) DepMap 22Q2 Public. figshare. Dataset. https://doi.org/10.6084/m9.figshare.19700056.v2
Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ, Colby CL, Therneau TM, Clark R, Kumar SK, Bradwell A, Fonseca R, Jelinek DF, Rajkumar SV (2010) Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet (london, England) 375(9727):1721–1728. https://doi.org/10.1016/S0140-6736(10)60482-5
Eisenberg E, Levanon EY (2013) Human housekeeping genes, revisited. Trends Genet 29(10):569–574. https://doi.org/10.1016/J.TIG.2013.05.010
Ferlay J, Ervik M, Lam F et al (2020) Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. https://gco.iarc.fr/today. Accessed 13 Jan 2023
Gautier L, Cope L, Bolstad BM, Irizarry RA (2004) affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics 20(3):307–315. https://doi.org/10.1093/bioinformatics/btg405
Grossman RL, Heath AP, Ferretti V, Varmus HE, Lowy DR, Kibbe WA, Staudt LM (2016) Toward a shared vision for cancer genomic data. N Engl J Med 375(12):1109–1112. https://doi.org/10.1056/NEJMP1607591
Kazandjian D (2016) Multiple myeloma epidemiology and survival, a unique malignancy. Semin Oncol 43(6):676. https://doi.org/10.1053/J.SEMINONCOL.2016.11.004
Kyle RA, Rajkumar SV (2008) Multiple myeloma. Blood 111(6):2962. https://doi.org/10.1182/BLOOD-2007-10-078022
Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, Melton LJ (2002) A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 346(8):564–569. https://doi.org/10.1056/NEJMOA01133202
Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A, Fonseca R, Rajkumar SV, Offord JR, Larson DR, Plevak ME, Therneau TM, Greipp PR (2003) Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 78(1):21–33. https://doi.org/10.4065/78.1.21
Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, Dispenzieri A, Katzmann JA, Melton LJ (2006) Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 354(13):1362–1369. https://doi.org/10.1056/NEJMOA054494
Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, Larson DR, Plevak MF, Jelinek DF, Fonseca R, Melton LJ, Rajkumar SV (2007) Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 356(25):2582–2590. https://doi.org/10.1056/NEJMOA070389
Landgren O, Graubard BI, Katzmann JA, Kyle RA, Ahmadizadeh I, Clark R, Kumar SK, Dispenzieri A, Greenberg AJ, Therneau TM, Melton LJ, Caporaso N, Korde N, Roschewski M, Costello R, McQuillan GM, Rajkumar SV (2014) Racial disparities in the prevalence of monoclonal gammopathies: a population-based study of 12,482 persons from the National Health and Nutritional Examination Survey. Leukemia 28(7):1537–1542. https://doi.org/10.1038/LEU.2014.34
Nair JR, Caserta J, Belko K, Howell T, Fetterly G, Baldino C, Lee KP (2017) Novel inhibition of PIM2 kinase has significant anti-tumor efficacy in multiple myeloma. Leukemia 31(8):1715–1726. https://doi.org/10.1038/LEU.2016.379
Neben K, Jauch A, Hielscher T, Hillengass J, Lehners N, Seckinger A, Granzow M, Raab MS, Ho AD, Goldschmidt H, Hose D (2013) Progression in smoldering myeloma is independently determined by the chromosomal abnormalities del(17p), t(4;14), gain 1q, hyperdiploidy, and tumor load. J Clin Oncol : Off J Am Soc Clin Oncol 31(34):4325–4332. https://doi.org/10.1200/JCO.2012.48.4923
Noone AM, Howlader N, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2023) SEER Cancer Statistics Review, 1975-2015, National Cancer Institute. Bethesda, MD. https://seer.cancer.gov/csr/1975_2015/
Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 364(11):1046–1060. https://doi.org/10.1056/NEJMRA1011442
Rajkumar SV (2019) Multiple myeloma: every year a new standard? Hematol Oncol 37(Suppl 1):62. https://doi.org/10.1002/HON.2586
Rajkumar SV, Gupta V, Fonseca R, Dispenzieri A, Gonsalves WI, Larson D, Ketterling RP, Lust JA, Kyle RA, Kumar SK (2013) Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia 27(8):1738–1744. https://doi.org/10.1038/LEU.2013.86
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK (2015) Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43(7):e47. https://doi.org/10.1093/NAR/GKV007
Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics, 2022. CA: A Cancer J Clin 72(1):7–33
Soliman AM, Das S, Teoh SL (2021) Next-generation biomarkers in multiple myeloma: understanding the molecular basis for potential use in diagnosis and prognosis. Int J Mol Sci 22(14). https://doi.org/10.3390/IJMS22147470
Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, Boutselakis H, Cole CG, Creatore C, Dawson E, Fish P, Harsha B, Hathaway C, Jupe SC, Kok CY, Noble K, Ponting L, Ramshaw CC, Rye CE, … Forbes SA (2019) COSMIC: the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res 47(D1):D941–D947. https://doi.org/10.1093/NAR/GKY1015
Therneau TM, Kyle RA, Melton LJ, Larson DR, Benson JT, Colby CL, Dispenzieri A, Kumar S, Katzmann JA, Cerhan JR, Rajkumar SV (2012) Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition. Mayo Clin Proc 87(11):1071–1079. https://doi.org/10.1016/J.MAYOCP.2012.06.014
van de Donk NWCJ, Pawlyn C, Yong KL (2021) Multiple myeloma. Lancet 397(10272):410–427. https://doi.org/10.1016/S0140-6736(21)00135-5
Weinstein JN, Collisson EA, Mills GB, Shaw KRM, Ozenberger B A, Ellrott K, Sander C, Stuart JM, Chang K, Creighton CJ, Davis C, Donehower L, Drummond J, Wheeler D, Ally A, Balasundaram M, Birol I, Butterfield YSN, Chu A., … Kling T (2013) The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet 45(10):1113–1120. https://doi.org/10.1038/NG.2764
Yang W, Soares J, Greninger P, Edelman EJ, Lightfoot H, Forbes S, Bindal N, Beare D, Smith JA, Thompson IR, Ramaswamy S, Futreal PA, Haber DA, Stratton M R, Benes C, McDermott U, Garnett MJ (2013) Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells. Nucleic Acids Res 41(D1). https://doi.org/10.1093/nar/gks1111
Zhang J, Baran J, Cros A, Guberman J, Database, S. H.-, undefined. (n.d.) (2011). International Cancer Genome Consortium Data Portal—a one-stop shop for cancer genomics data. Academic.Oup.Com. Retrieved January 18, 2023, from https://academic.oup.com/database/article-abstract/doi/https://doi.org/10.1093/database/bar026/465210
Acknowledgements
AK, KVK, and KK acknowledge the fellowship from Ministry of Education, Government of India. AS acknowledge the fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. RK is thankful to the Indian Institute of Technology Hyderabad for providing research infrastructure.
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Financial support for research infrastructure was provided by the Indian Institute of Technology Hyderabad.
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AK, KVK, and RK conceived the idea and prepared the database framework. AK and KVK collected and analyzed the datasets. AK developed the database and wrote the first draft of the manuscript. KK, AS, KR, and SS helped in collecting the datasets and preparing the database outline. All authors read the manuscript and approved it for submission.
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Kumar, A., Kumar, K.V., Kundal, K. et al. MyeloDB: a multi-omics resource for multiple myeloma. Funct Integr Genomics 24, 17 (2024). https://doi.org/10.1007/s10142-023-01280-0
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DOI: https://doi.org/10.1007/s10142-023-01280-0