Machine Learning-Enhanced Extraction of Biomarkers for High-Grade Serous Ovarian Cancer from Proteomics Data.

Comprehensive biomedical proteomic datasets are accumulating exponentially, warranting robust analytics to deconvolute them for identifying novel biological insights. Here, we report a strategic machine learning (ML)-based feature extraction workflow that was applied to unveil high-performing protein markers for high-grade serous ovarian carcinoma (HGSOC) from publicly available ovarian cancer tissue and serum proteomics datasets. Diagnosis of HGSOC, an aggressive form of ovarian cancer, currently relies on diagnostic methods based on tissue biopsy and/or non-specific biomarkers such as the cancer antigen 125 (CA125) and human epididymis protein 4 (HE4).

FlexStat: combinatory differentially expressed protein extraction.

Motivation: Mass spectrometry-based system proteomics allows identification of dysregulated protein hubs and associated disease-related features. Obtaining differentially expressed proteins (DEPs) is the most important step of downstream bioinformatics analysis. However, the extraction of statistically significant DEPs from datasets with multiple experimental conditions or disease types through currently available tools remains a laborious task.

Potential relevance of salivary legumain for the clinical diagnostic of hand, foot, and mouth disease.

The fight against hand, foot, and mouth disease (HFMD) remains an arduous challenge without existing point-of-care (POC) diagnostic platforms for accurate diagnosis and prompt case quarantine. Hence, the purpose of this salivary biomarker discovery study is to set the fundamentals for the realization of POC diagnostics for HFMD. Whole salivary proteome profiling was performed on the saliva obtained from children with HFMD and healthy children, using a reductive dimethylation chemical labeling method coupled with high-resolution mass spectrometry-based quantitative proteomics technology.

Multiomics analyses reveal dynamic bioenergetic pathways and functional remodeling of the heart during intermittent fasting.

Intermittent fasting (IF) has been shown to reduce cardiovascular risk factors in both animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction. However, the underlying molecular mechanisms behind these effects remain unclear. To shed light on the molecular and cellular adaptations of the heart to IF, we conducted comprehensive system-wide analyses of the proteome, phosphoproteome, and transcriptome, followed by functional analysis.

System-wide vitreous proteome dissection reveals impaired sheddase activity in diabetic retinopathy.

Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. DR is a multifactorial disease involving changes in retinal microvasculature and neuronal layers, and aberrations in vascular endothelial growth factors (VEGF) and inflammatory pathways. Despite the success of anti-VEGF therapy, many DR patients do not respond well to the treatment, emphasizing the involvement of other molecular players in neuronal and vascular aberrations in DR.

Englerin A Rewires Phosphosignaling via Hsp27 Hyperphosphorylation to Induce Cytotoxicity in Renal Cancer Cells.

Englerin A (EA) is a small-molecule natural product with selective cytotoxicity against renal cancer cells. EA has been shown to induce apoptosis and cell death through cell-cycle arrest and/or insulin signaling pathways. However, its biological mode of action or targets in renal cancer remains enigmatic.

Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain.

Intermittent fasting (IF) remains the most effective intervention to achieve robust anti-aging effects and attenuation of age-related diseases in various species. Epigenetic modifications mediate the biological effects of several environmental factors on gene expression; however, no information is available on the effects of IF on the epigenome. Here, we first found that IF for 3 months caused modulation of H3K9 trimethylation (H3K9me) in the cerebellum, which in turn orchestrated a plethora of transcriptomic changes involved in robust metabolic switching processes commonly observed during IF.

Comprehensive Proteomic Characterization Reveals Subclass-Specific Molecular Aberrations within Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer lacking targeted therapies. This is attributed to its high heterogeneity that complicates elucidation of its molecular aberrations. Here, we report identification of specific proteome expression profiles pertaining to two TNBC subclasses, basal A and basal B, through in-depth proteomics analysis of breast cancer cells.

Pilot Study of Renal Urinary Biomarkers for Diagnosis of CKD of Uncertain Etiology.

Introduction: Chronic kidney disease of uncertain etiology (CKDu), an emerging chronic kidney disease (CKD) subtype, contributes to significant morbidity and mortality in certain tropical countries. Although several indicators of CKDu have been previously suggested, sensitive and specific tests to detect early disease or predict disease progression are currently unavailable. This study focused on evaluating 8 renal urinary markers, namely neutrophil gelatinase-associated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM1), cystatin C (CST3), beta 2 microglobulin (B2M), osteopontin (OPN), alpha 1 microglobulin (A1M), tissue inhibitor of metalloproteinase 1 (TIMP1), and retinol binding protein 4 (RBP4), with the hypothesis that these have distinct expression patterns in patients with CKDu.

Genome-Wide Transcriptome Analysis Reveals Intermittent Fasting-Induced Metabolic Rewiring in the Liver.

Intermittent fasting (IF) has been extensively reported to promote improved energy homeostasis and metabolic switching. While IF may be a plausible strategy to ameliorate the epidemiological burden of disease in many societies, our understanding of the underlying molecular mechanisms behind such effects is still lacking. The present study has sought to investigate the relationship between IF and changes in gene expression.

Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade.

Internal-tamponade agents are crucial surgical adjuncts in vitreoretinal surgery. Clinically used endotamponade agents act through buoyancy forces, yet can result in prolonged post-operative positioning, temporary loss of vision, raised intra-ocular pressure, cataract formation or the need for additional removal surgery. Here, we describe a thermogelling polymer that provides an internal tamponade effect through surface tension and swelling counter-forces.

Multiplex targeted mass spectrometry assay for one-shot flavivirus diagnosis.

Targeted proteomic mass spectrometry is emerging as a salient clinical diagnostic tool to track protein biomarkers. However, its strong analytical properties have not been exploited in the diagnosis and typing of flaviviruses. Here, we report the development of a sensitive and specific single-shot robust assay for flavivirus typing and diagnosis using targeted mass spectrometry technology.

Phosphoproteomics reveals network rewiring to a pro-adhesion state in annexin-1-deficient mammary epithelial cells.

Background: Annexin-1 (ANXA1) plays pivotal roles in regulating various physiological processes including inflammation, proliferation and apoptosis, and deregulation of ANXA1 functions has been associated with tumorigenesis and metastasis events in several types of cancer. Though ANXA1 levels correlate with breast cancer disease status and outcome, its distinct functional involvement in breast cancer initiation and progression remains unclear. We hypothesized that ANXA1-responsive kinase signaling alteration and associated phosphorylation signaling underlie early events in breast cancer initiation events and hence profiled ANXA1-dependent phosphorylation changes in mammary gland epithelial cells.

Deubiquitinating Enzyme USP9X Suppresses Tumor Growth via LATS Kinase and Core Components of the Hippo Pathway.

The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway.

Phosphoprotein network analysis of white adipose tissues unveils deregulated pathways in response to high-fat diet.

Despite efforts in the last decade, signaling aberrations associated with obesity remain poorly understood. To dissect molecular mechanisms that define this complex metabolic disorder, we carried out global phosphoproteomic analysis of white adipose tissue (WAT) from mice fed on low-fat diet (LFD) and high-fat diet (HFD). We quantified phosphorylation levels on 7696 peptides, and found significant differential phosphorylation levels in 282 phosphosites from 191 proteins, including various insulin-responsive proteins and metabolic enzymes involved in lipid homeostasis in response to high-fat feeding.

Functional mapping of the zebrafish early embryo proteome and transcriptome.

Zebrafish is a popular system for studying vertebrate development and disease that shows high genetic conservation with humans. Molecular level studies at different stages of development are essential for understanding the processes deployed during ontogeny. Here, we performed comparative analysis of the whole proteome and transcriptome of the early stage (24 h post-fertilization) zebrafish embryo.

Mass spectrometry based quantitative proteomics and integrative network analysis accentuates modulating roles of annexin-1 in mammary tumorigenesis.

Annexin-1 (ANXA1) is known to be involved in important cellular processes and implicated in cancer. Our previous study showed its roles in cell migration and DNA-damage response processes in breast cancer initiation. In order to understand its roles in tumorigenesis, we extended our studies to analyze tumors derived from polyomavirus middle T-antigen ANXA1 heterozygous (ANXA1(+/-) ) and ANXA1 null (ANXA1(-/-) ) mice.