The Need for Multi-Omics Biomarker Signatures in Precision Medicine

Olivier, Michael; Asmis, Reto; Hawkins, Gregory A.; Howard, Timothy D.; Cox, Laura A.

doi:10.3390/ijms20194781

Cited by 351 publications

(256 citation statements)

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“…Cancer involves a complex regulatory network, and therefore integrating multiple omics data is required in the era of precision medicine (Olivier et al, 2019). The increasing applications of multi-omic profiling of GC have delivered new insight into the dynamics of this cancer type.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Identification and Characterization of DNA Methylation and Long Non-Coding RNA Expression in Gastric Cancer

Song

Guan

2020

Front. Genet.

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Abnormal DNA methylation, an epigenetic modification, has increasingly been linked to the pathogenesis of many human cancers. However, there has been little focus on the DNA methylation patterns of genes encoding long noncoding RNAs (lncRNAs) in gastric cancer (GC). This study comprehensively determined DNA methylation and lncRNA expression profiles in GC through genome-wide analysis. Differentially methylated loci and lncRNAs were identified by integrating multi-omics data. In total, 548 differentially methylated CpG sites in lncRNA promoters and 2,399 differentially expressed lncRNAs were screened that were capable of distinguishing GC from normal tissues. Among them, 22 differentially methylation sites in 17 lncRNAs were inversely related to expression levels. Further analysis of DNA methylation status and gene expression level in GC revealed that three CpG sites (cg01550148, cg22497867, and cg20001829) and two lncRNAs (RP11-366F6.2 and RP5-881L22.5) were significantly associated with GC patient overall survival. Molecular function analysis showed that these abnormally methylated lncRNAs were mainly involved in transcriptional activator activity. Our study identified several lncRNAs regulated by aberrant DNA methylation that have clinical utility as novel prognostic biomarkers in GC. These findings help improve the understanding of methylated patterns of lncRNAs and further our knowledge of the role of epigenetics in cancer development.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Identification and Characterization of DNA Methylation and Long Non-Coding RNA Expression in Gastric Cancer

Song

Guan

2020

Front. Genet.

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“…Adding either of these approaches transforms the platform into a scalable quantitative method that allows one to compare relative target intensities between samples within large cohorts. This is advantageous when screening for disease biomarkers, stratifying patients within a particular disease group [70], or monitoring point mutations that frequently arise to confer drug resistance [71].…”

Section: Discussionmentioning

confidence: 99%

Affinity-Bead Assisted Mass Spectrometry (Affi-BAMS): A Multiplexed Microarray Platform for Targeted Proteomics

Hamza

Bergo

Mamaev

et al. 2020

IJMS

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The ability to quantitatively probe diverse panels of proteins and their post-translational modifications (PTMs) across multiple samples would aid a broad spectrum of biological, biochemical and pharmacological studies. We report a novel, microarray analytical technology that combines immuno-affinity capture with Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI MS), which is capable of supporting highly multiplexed, targeted proteomic assays. Termed “Affinity-Bead Assisted Mass Spectrometry” (Affi-BAMS), this LC-free technology enables development of highly specific and customizable assay panels for simultaneous profiling of multiple proteins and PTMs. While affinity beads have been used previously in combination with MS, the Affi-BAMS workflow uses enrichment on a single bead that contains one type of antibody, generally capturing a single analyte (protein or PTM) while having enough binding capacity to enable quantification within approximately 3 orders of magnitude. The multiplexing capability is achieved by combining Affi-BAMS beads with different protein specificities. To enable screening of bead-captured analytes by MS, we further developed a novel method of performing spatially localized elution of targets from individual beads arrayed on a microscope slide. The resulting arrays of micro spots contain highly concentrated analytes localized within 0.5 mm diameter spots that can be directly measured using MALDI MS. While both intact proteins and protein fragments can be monitored by Affi-BAMS, we initially focused on applying this technology for bottom-up proteomics to enable screening of hundreds of samples per day by combining the robust magnetic bead-based workflow with the high throughput nature of MALDI MS acquisition. To demonstrate the variety of applications and robustness of Affi-BAMS, several studies are presented that focus on the response of 4EBP1, RPS6, ERK1/ERK2, mTOR, Histone H3 and C-MET to stimuli including rapamycin, H2O2, EPO, SU11274, Staurosporine and Vorinostat.

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“…Future issues will collect more multiomics-based molecular network studies with large-scale clinical information for basic research, translational research, and clinical practice in pituitary adenomas. We strongly believe that multiomics-based molecular network studies, molecular network-based therapeutic target and drug studies, and molecular network-based pattern biomarker studies (5,10,11,13,(32)(33)(34)(35)(36)(37) will bring a brighter future for pituitary adenoma patients through the realization of personalized and precision medicine.…”

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confidence: 99%