In Silico Methods for the Identification of Diagnostic and Favorable Prognostic Markers in Acute Myeloid Leukemia.
Hande YılmazHalil Ibrahim ToyStephan MarquardtGökhan KarakülahCan KüçükPanagiota I KontouStella LogothetiAthanasia PavlopoulouPublished in: International journal of molecular sciences (2021)
Acute myeloid leukemia (AML), the most common type of acute leukemia in adults, is mainly asymptomatic at early stages and progresses/recurs rapidly and frequently. These attributes necessitate the identification of biomarkers for timely diagnosis and accurate prognosis. In this study, differential gene expression analysis was performed on large-scale transcriptomics data of AML patients versus corresponding normal tissue. Weighted gene co-expression network analysis was conducted to construct networks of co-expressed genes, and detect gene modules. Finally, hub genes were identified from selected modules by applying network-based methods. This robust and integrative bioinformatics approach revealed a set of twenty-four genes, mainly related to cell cycle and immune response, the diagnostic significance of which was subsequently compared against two independent gene expression datasets. Furthermore, based on a recent notion suggesting that molecular characteristics of a few, unusual patients with exceptionally favorable survival can provide insights for improving the outcome of individuals with more typical disease trajectories, we defined groups of long-term survivors in AML patient cohorts and compared their transcriptomes versus the general population to infer favorable prognostic signatures. These findings could have potential applications in the clinical setting, in particular, in diagnosis and prognosis of AML.
Keyphrases
- network analysis
- acute myeloid leukemia
- genome wide identification
- genome wide
- bioinformatics analysis
- cell cycle
- dna methylation
- gene expression
- transcription factor
- allogeneic hematopoietic stem cell transplantation
- immune response
- single cell
- genome wide analysis
- copy number
- cell proliferation
- newly diagnosed
- poor prognosis
- prognostic factors
- ejection fraction
- rna seq
- machine learning
- patient reported outcomes
- high resolution
- depressive symptoms
- dendritic cells
- magnetic resonance
- magnetic resonance imaging
- molecular dynamics simulations
- big data