An Integrative Computational Approach to Evaluate Genetic Markers for Chronic Lymphocytic Leukemia

Overview

Journal J Comput Biol

Specialties Biology
Molecular Biology

Date 2017 Jun 2

PMID 28570130

Authors

Yu Zheng

Xiaoyang Li

Lydia C Manor

Hongbao Cao

Qiusheng Chen

Affiliations

Soon will be listed here.

Abstract

Recent studies reported hundreds of genes linked to chronic lymphocytic leukemia (CLL). However, many of these candidate genes were lack of replication and results were not always consistent. Here, we proposed a computational workflow to curate and evaluate CLL-related genes. The method integrates large-scale literature knowledge data, gene expression data, and related pathways/network information for quantitative marker evaluation. Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four metrics proposed and validated for each gene. By using our approach, a scalable CLL genetic database was developed including CLL-related genes, pathways, diseases and information of supporting references. The CLL case/control classification supported the effectiveness of the four proposed metrics, which successfully identified nine well-studied CLL genes (i.e., TNF, BCL2, TP53, VEGFA, P2RX7, AKT1, SYK, IL4, and MDM2) and highlighted two newly reported CLL genes (i.e., PDGFRA and CSF1R). The computational biology approach and the CLL database developed in this study provide a valuable resource that may facilitate the understanding of the genetic profile of CLL.

References

Friedrichs B, Siegel S, Kloess M, Barsoum A, Coggin Jr J, Rohrer J . Humoral immune responses against the immature laminin receptor protein show prognostic significance in patients with chronic lymphocytic leukemia. J Immunol. 2008; 180(9):6374-84. DOI: 10.4049/jimmunol.180.9.6374. View

Lu Y, Goldstein D, Angrist M, Cavalleri G . Personalized medicine and human genetic diversity. Cold Spring Harb Perspect Med. 2014; 4(9):a008581. PMC: 4143101. DOI: 10.1101/cshperspect.a008581. View

Baumer A, Freyhaus H, Sauer H, Wartenberg M, Kappert K, Schnabel P . Phosphatidylinositol 3-kinase-dependent membrane recruitment of Rac-1 and p47phox is critical for alpha-platelet-derived growth factor receptor-induced production of reactive oxygen species. J Biol Chem. 2007; 283(12):7864-76. DOI: 10.1074/jbc.M704997200. View

Messmer B, Messmer D, Allen S, Kolitz J, Kudalkar P, Cesar D . In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest. 2005; 115(3):755-64. PMC: 548318. DOI: 10.1172/JCI23409. View

Davids M, Brown J . Phosphoinositide 3'-kinase inhibition in chronic lymphocytic leukemia. Hematol Oncol Clin North Am. 2013; 27(2):329-39. PMC: 3615463. DOI: 10.1016/j.hoc.2012.12.002. View

Mauro F, Foa R, Giannarelli D, Cordone I, Crescenzi S, Pescarmona E . Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases. Blood. 1999; 94(2):448-54. View

Lorenzi P, Claerhout S, Mills G, Weinstein J . A curated census of autophagy-modulating proteins and small molecules: candidate targets for cancer therapy. Autophagy. 2014; 10(7):1316-26. PMC: 4203555. DOI: 10.4161/auto.28773. View

Hojjat-Farsangi M, Khan A, Daneshmanesh A, Moshfegh A, Sandin A, Mansouri L . The tyrosine kinase receptor ROR1 is constitutively phosphorylated in chronic lymphocytic leukemia (CLL) cells. PLoS One. 2013; 8(10):e78339. PMC: 3813472. DOI: 10.1371/journal.pone.0078339. View

Quiney C, Dauzonne D, Kern C, Fourneron J, Izard J, Mohammad R . Flavones and polyphenols inhibit the NO pathway during apoptosis of leukemia B-cells. Leuk Res. 2004; 28(8):851-61. DOI: 10.1016/j.leukres.2003.12.003. View

10.

Demir H, Bayhan T, Uner A, Kurtulan O, Karakus E, Emir S . Chronic lymphocytic leukemia in a child: a challenging diagnosis in pediatric oncology practice. Pediatr Blood Cancer. 2013; 61(5):933-5. DOI: 10.1002/pbc.24865. View

11.

Sivachenko A, Yuryev A, Daraselia N, Mazo I . Molecular networks in microarray analysis. J Bioinform Comput Biol. 2007; 5(2B):429-56. DOI: 10.1142/s0219720007002795. View

12.

Herishanu Y, Perez-Galan P, Liu D, Biancotto A, Pittaluga S, Vire B . The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood. 2010; 117(2):563-74. PMC: 3031480. DOI: 10.1182/blood-2010-05-284984. View

13.

Rosen S, Maciorowski Z, Wittlin F, Epstein A, Gordon L, Kies M . Estrogen receptor analysis in chronic lymphocytic leukemia. Blood. 1983; 62(5):996-9. View

14.

Daraselia N, Yuryev A, Egorov S, Novichkova S, Nikitin A, Mazo I . Extracting human protein interactions from MEDLINE using a full-sentence parser. Bioinformatics. 2004; 20(5):604-11. DOI: 10.1093/bioinformatics/btg452. View

15.

Paterson A, Mockridge C, Adams J, Krysov S, Potter K, Duncombe A . Mechanisms and clinical significance of BIM phosphorylation in chronic lymphocytic leukemia. Blood. 2011; 119(7):1726-36. DOI: 10.1182/blood-2011-07-367417. View

16.

Galletti G, Caligaris-Cappio F, Bertilaccio M . B cells and macrophages pursue a common path toward the development and progression of chronic lymphocytic leukemia. Leukemia. 2016; 30(12):2293-2301. DOI: 10.1038/leu.2016.261. View

17.

Billard C . Apoptosis inducers in chronic lymphocytic leukemia. Oncotarget. 2014; 5(2):309-25. PMC: 3964209. DOI: 10.18632/oncotarget.1480. View

18.

Rieger A, Havixbeck J, Belosevic M, Barreda D . Teleost soluble CSF-1R modulates cytokine profiles at an inflammatory site, and inhibits neutrophil chemotaxis, phagocytosis, and bacterial killing. Dev Comp Immunol. 2014; 49(2):259-66. DOI: 10.1016/j.dci.2014.12.003. View

19.

Shanshal M, Haddad R . Chronic lymphocytic leukemia. Dis Mon. 2012; 58(4):153-67. DOI: 10.1016/j.disamonth.2012.01.009. View

20.

Wang J, Cao H, Liao Y, Liu W, Tan L, Tang Y . Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings. Neuroimage Clin. 2015; 8:95-103. PMC: 4473730. DOI: 10.1016/j.nicl.2015.03.017. View