Molecular Omics

Choudhury, Priyanka; Dasgupta, Sanjukta; Bhattacharyya, Parthasarathi; Roychowdhury, Sushmita; Chaudhury, Koel

doi: 10.1039/d3mo00266gpmid: 38853716

Pulmonary hypertension (PH), characterised by mean pulmonary arterial pressure (mPAP) >20 mm Hg at rest, is a complex pathophysiological disorder associated with multiple clinical conditions. The high prevalence of the disease along with increased mortality and morbidity makes it a global health burden. Despite major advances in understanding the disease pathophysiology, much of the underlying complex molecular mechanism remains to be elucidated. Lack of a robust diagnostic test and specific therapeutic targets also poses major challenges. This review provides a comprehensive update on the dysregulated pathways and promising candidate markers identified in PH patients using the transcriptomics and metabolomics approach. The review also highlights the need of using an integrative multi-omics approach for obtaining insight into the disease at a molecular level. The integrative multi-omics/pan-omics approach envisaged to help in bridging the gap from genotype to phenotype is outlined. Finally, the challenges commonly encountered while conducting omics-driven studies are also discussed.

Chakraborty, Aishani; Alsharqi, Leila; Kostrzewa, Markus; Armstrong-James, Darius; Larrouy-Maumus, Gerald

doi: 10.1039/d4mo00030gpmid: 38623711

Glycosyl-inositol-phospho-ceramides (GIPCs) or glycosylphosphatidylinositol-anchored fungal polysaccharides are major lipids in plant and fungal plasma membranes and play an important role in stress adaption. However, their analysis remains challenging due to the multiple steps involved in their extraction and purification prior to mass spectrometry analysis. To address this challenge, we report here a novel simplified method to identify GIPCs from Aspergillus fumigatus using the new Bruker MBT lipid Xtract assay. A. fumigatus reference strains and clinical isolates were cultured, harvested, heat-inactivated and suspended in double-distilled water. A fraction of this fungal preparation was then dried in a microtube, mixed with an MBT lipid Xtract matrix (Bruker Daltonik, Germany) and loaded onto a MALDI target plate. Analysis was performed using a Bruker MALDI Biotyper Sirius system in the linear negative ion mode. Mass spectra were scanned from m/z 700 to m/z 2 000. MALDI-TOF MS analysis of cultured fungi showed a clear signature of GIPCs in Aspergillus fumigatus reference strains and clinical isolates. Here, we have demonstrated that routine MALDI-TOF in the linear negative ion mode combined with the MBT lipid Xtract is able to detect Aspergillus fumigatus GIPCs.

Güven Gülhan, Ünzile; Nikerel, Emrah; Çakır, Tunahan; Erdoğan Sevilgen, Fatih; Durmuş, Saliha

doi: 10.1039/d4mo00016apmid: 38780313

Enterotypes have been shown to be an important factor for population stratification based on gut microbiota composition, leading to a better understanding of human health and disease states. Classifications based on compositional patterns will have implications for personalized microbiota-based solutions. There have been limited enterotype based studies on colorectal adenoma and cancer. Here, an enterotype-based meta-analysis of fecal shotgun metagenomic studies was performed, including 1579 samples of healthy controls (CTR), colorectal adenoma (ADN) and colorectal cancer (CRC) in total. Gut microbiota of healthy people were clustered into three enterotypes (Ruminococcus-, Bacteroides- and Prevotella-dominated enterotypes). Reference-based enterotype assignments were performed for CRC and ADN samples, using the supervised machine learning algorithm, K-nearest neighbors. Differential abundance analyses and random forest classification were conducted on each enterotype between healthy controls and CRC–ADN groups, revealing novel enterotype-specific microbial markers for non-invasive CRC screening strategies. Furthermore, we identified microbial species unique to each enterotype that play a role in the production of secondary bile acids and short-chain fatty acids, unveiling the correlation between cancer-associated gut microbes and dietary patterns. The enterotype-based approach in this study is promising in elucidating the mechanisms of differential gut microbiome profiles, thereby improving the efficacy of personalized microbiota-based solutions.

Xu, Zhi; Miao, Rui; Han, Tao; Liu, Yafeng; Zhou, Jiawei; Guo, Jianqiang; Xing, Yingru; Bai, Ying; Wu, Jing; Hu, Dong

doi: 10.1039/d4mo00044gpmid: 38940931

Objective: this study evaluates the prognostic relevance of gene subtypes and the role of kinesin family member 2C (KIF2C) in lung cancer progression. Methods: high-expression genes linked to overall survival (OS) and progression-free interval (PFI) were selected from the TCGA-LUAD dataset. Consensus clustering analysis categorized lung adenocarcinoma (LUAD) patients into two subtypes, C1 and C2, which were compared using clinical, drug sensitivity, and immunotherapy analyses. A random forest algorithm pinpointed KIF2C as a prognostic hub gene, and its functional impact was assessed through various assays and in vivo experiments. Results: The study identified 163 key genes and distinguished two LUAD subtypes with differing OS, PFI, pathological stages, drug sensitivity, and immunotherapy response. KIF2C, highly expressed in the C2 subtype, was associated with poor prognosis, promoting cancer cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), with knockdown reducing tumor growth in mice. Conclusion: The research delineates distinct LUAD subtypes with significant clinical implications and highlights KIF2C as a potential therapeutic target for personalized treatment in LUAD.

doi: 10.1039/d4mo90018apmid: N/A