Integrative Analysis of DiseaseLand Omics Database for Disease Signatures and Treatments: A Bipolar Case Study

Abstract

Transcriptomics technologies such as next-generation sequencing and microarray platforms provide exciting opportunities for improving diagnosis and treatment of complex diseases. Transcriptomics studies often share similar hypotheses, but are carried out on different platforms, in different conditions, and with different analysis approaches. These factors, in addition to small sample sizes, can result in a lack of reproducibility. A clear understanding and unified picture of many complex diseases are still elusive, highlighting an urgent need to effectively integrate multiple transcriptomic studies for disease signatures. We have integrated more than 3,000 high-quality transcriptomic datasets in oncology, immunology, neuroscience, cardiovascular and metabolic disease, and from both public and internal sources (DiseaseLand database). We established a systematic data integration and meta-analysis approach, which can be applied in multiple disease areas to create a unified picture of the disease signature and prioritize drug targets, pathways, and compounds. In this bipolar case study, we provided an illustrative example using our approach to combine a total of 30 genome-wide gene expression studies using postmortem human brain samples. First, the studies were integrated by extracting raw FASTQ or CEL files, then undergoing the same procedures for preprocessing, normalization, and statistical inference. Second, both p -value and effect size based meta-analysis algorithms were used to identify a total of 204 differentially expressed (DE) genes (FDR < 0.05) genes in the prefrontal cortex. Among these were BDNF , VGF , WFS1 , DUSP6 , CRHBP , MAOA , and RELN , which have previously been implicated in bipolar disorder. Finally, pathway enrichment analysis revealed a role for GPCR, MAPK, immune, and Reelin pathways. Compound profiling analysis revealed MAPK and other inhibitors may modulate the DE genes. The ability to robustly combine and synthesize the information from multiple studies enables a more powerful understanding of this complex disease.

Identification of novel cell glycolysis related gene signature predicting survival in patients with breast cancer

“…The Warburg influence has emerged in multiple malignant cancers, such as lung cancer, prostate cancer, pancreatic cancer and colon cancer, following more than 90 years of continuing study and testing. Recent findings have shown that aerobic glycolysis plays a significant function in the growth of BC 28 . Metabolism in BC cells showed a higher glycolysis rate and a lower glucose oxidation rate.…”

Genome-wide association study analysis of disease severity in Acne reveals novel biological insights

“…Several studies have delved into the exploration of integrated transcriptomics data through various meta-analyses 48,49 . We opted for the Fisher’s exact test for its straightforward implementation, heightened sensitivity to small sample sizes, non-parametric nature, and platform independence across transcriptomics techniques (such as microarray and RNA-seq).…”

“…Differential gene expressions (DGE) were extracted from integrated transcriptomics service from Qiagen Omicsoft database (QIAGEN OmicSoft DiseaseLand 47 ). We extracted both microarray and RNA-seq based transcriptomic (TxP) studies and disease comparisons/contrasts available for all studies in the DiseaseLand in the immunology and inflammation, Internal neurodegenerative and metabolic diseases 48 . Common ontologies were applied to all samples, tissues, diseases, treatments, and comparison types to systematize database curation.…”

“…The copyright holder for this this version posted November 14, 2023. ; https://doi.org/10.1101/2023.11.13.23298473 doi: medRxiv preprint Internal neurodegenerative and metabolic diseases 48 . Common ontologies were applied to all samples, tissues, diseases, treatments, and comparison types to systematize database curation.…”

HOXB9 Overexpression Promotes Colorectal Cancer Progression and Is Associated with Worse Survival in Liver Resection Patients for Colorectal Liver Metastases

“…The UALCAN online platform (http://ualcan.path.uab.edu/, (accessed on 23 December 2021) was used to compare the transcriptional levels of HOXB9 in CRC compared to other types of cancers and the GEPIA tool (http://gepia.cancer-pku.cn/index.html, (accessed on 27 December 2021)) was used to compare the transcriptional levels of HOXB9 in CRC in comparison with the rest of the HOX genes [17][18][19]. Lastly, the OmicSoft Suite with the integrated OncoLand database (Qiagen, Manchester, UK) was used to assess the HOXB9 gene expression levels in CRC mutant versus wild-type for the top three somatic mutations in CRC which were identified using the COSMIC database (https://cancer.sanger.ac.uk/cosmic, (accessed on 22 June 2020)) [20].…”