Mass spectrometry proteomic diagnosis: enacting the validation paradigm

The rapidly expanding field of metabolomics presents an invaluable resource for understanding the associations between metabolites and various diseases. However, the high dimensionality, presence of missing values, and measurement errors associated with metabolomics data can present challenges in developing reliable and reproducible methodologies for disease association studies. Therefore, there is a compelling need to develop robust statistical methods that can navigate thes...

Motivation: Assigning statistical significance accurately has become increasingly important as meta data of many types, often assembled in hierarchies, are constructed and combined for further biological analyses. Statistical inaccuracy of meta data at any level may propagate to downstream analyses, undermining the validity of scientific conclusions thus drawn. From the perspective of mass spectrometry based proteomics, even though accurate statistics for peptide identificati...

Recent advances in experimental methods have enabled researchers to collect data on thousands of analytes simultaneously. This has led to correlational studies that associated molecular measurements with diseases such as Alzheimer's, Liver, and Gastric Cancer. However, the use of thousands of biomarkers selected from the analytes is not practical for real-world medical diagnosis and is likely undesirable due to potentially formed spurious correlations. In this study, we evalu...

The histological assessment of human tissue has emerged as the key challenge for detection and treatment of cancer. A plethora of different data sources ranging from tissue microarray data to gene expression, proteomics or metabolomics data provide a detailed overview of the health status of a patient. Medical doctors need to assess these information sources and they rely on data driven automatic analysis tools. Methods for classification, grouping and segmentation of heterog...

In high-dimensional prediction settings, it remains challenging to reliably estimate the test performance. To address this challenge, a novel performance estimation framework is presented. This framework, called Learn2Evaluate, is based on learning curves by fitting a smooth monotone curve depicting test performance as a function of the sample size. Learn2Evaluate has several advantages compared to commonly applied performance estimation methodologies. Firstly, a learning cur...

Building prediction models from mass-spectrometry data is challenging due to the abundance of correlated features with varying degrees of zero-inflation, leading to a common interest in reducing the features to a concise predictor set with good predictive performance. In this study, we formally established and examined regularized regression approaches, designed to address zero-inflated and correlated predictors. In particular, we describe a novel two-stage regularized regres...

The success of metabolomics studies depends upon the "fitness" of each biological sample used for analysis: it is critical that metabolite levels reported for a biological sample represent an accurate snapshot of the studied organism's metabolite profile at time of sample collection. Numerous factors may compromise metabolite sample fitness, including chemical and biological factors which intervene during sample collection, handling, storage, and preparation for analysis. We ...

Discovery of novel protein biomarkers for clinical applications is an active research field across a manifold of diseases. Despite some successes and progress, the biomarker development pipeline still frequently ends in failure as biomarker candidates cannot be validated or translated to immunoassays. Selection of strong disease biomarker candidates that further constitute suitable targets for antibody binding in immunoassays is thus important. This essential selection step c...

Research in the life sciences often employs messenger ribonucleic acids (mRNA) quantification as a standalone approach for functional analysis. However, although the correlation between the measured levels of mRNA and proteins is positive, correlation coefficients observed empirically are incomplete, necessitating caution in making agnostic inferences. This essay provides a statistical reflection and caveat on the concept of correlation strength in the context of transcriptom...

The human-associated microbiome is closely tied to human health and is of substantial clinical interest. Metagenomics-based tools are emerging for clinical diagnostics, tracking the spread of diseases, and surveillance of potential pathogens. In some cases, these tools are overcoming limitations of traditional clinical approaches. Metagenomics has limitations barring the tools from clinical validation. Once these hurdles are overcome, clinical metagenomics will inform doctors...