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Ho-Joon Lee

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Dr. Lee’s research in data science concerns biological questions in systems biology and network medicine by developing algorithms and models through a combination of statistical/machine learning, information theory, and network theory applied to multi-dimensional large-scale data. His projects have covered genomics, transcriptomics, proteomics, and metabolomics from yeast to mouse to human for integrative analysis of regulatory networks on multiple molecular levels, which also incorporates large-scale public databases such as GO for functional annotation, PDB for molecular structures, and PubChem and LINCS for drugs or small compounds. He previously carried out proteomics and metabolomics along with a computational derivation of dynamic protein complexes for IL-3 activation and cell cycle in murine pro-B cells (Lee et al., Cell Reports 2017), for which he developed integrative analytical tools using diverse approaches from machine learning and network theory. His ongoing interests in methodology include machine/deep learning and topological Kolmogorov-Sinai entropy-based network theory, which are applied to (1) multi-level dynamic regulatory networks in immune response, cell cycle, and cancer metabolism and (2) mass spectrometry-based omics data analysis.

Figure 1. Proteomics and metabolomics analysis of IL-3 activation and cell cycle (Lee et al., Cell Reports 2017). (A) Multi-omics abundance profiles of proteins, modules/complexes, intracellular metabolites, and extracellular metabolites over one cell cycle (from left to right columns) in response to IL-3 activation. Red for proteins/modules/intracellular metabolites up-regulation or extracellular metabolites release; Green for proteins/modules/intracellular metabolites down-regulation or extracellular metabolites uptake. (B) Functional module network identified from integrative analysis. Red nodes are proteins and white nodes are functional modules. Expression profile plots are shown for literature-validated functional modules. (C) Overall pathway map of IL-3 activation and cell cycle phenotypes. (D) IL-3 activation and cell cycle as a cancer model along with candidate protein and metabolite biomarkers. (E) Protein co-expression scale-free network. (F) Power-low degree distribution of the network E. (G) Protein entropy distribution by topological Kolmogorov-Sinai entropy calculated for the network E.

 

Santiago Schnell

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Dr. Schnell works at the interface between biophysical chemistry, mathematical and computational biology, and pathophysiology. As an independent scientist, his primary research interest is to use mathematical, computational and statistical methods to design or select optimal procedures and experiments, and to provide maximum information by analyzing biochemical data. His laboratory deals with the following topics:

(i) Development and implementation of mathematical, computational, and statistical methods to identify and characterize reaction mechanisms.

(ii) Investigate and test performance design of experiments or standards to quantify, interpret and analyze biochemical data.

(iii) Development of new algorithms and software to analyze biochemical data.

The key objective of my research is to create suitable standards and appropriate support of standards leading to reproducible results in the biochemical sciences. Reproducibility is central to scientific credibility. Meta-research has repeatedly shown that accurate reporting and sound peer-review do not by themselves guarantee the reproducibility of scientific results. One of the leading causes of poor reproducibility is limited research efforts in quantitative biology and chemometrics. In my laboratory, we are developing new ways to assess the reproducibility of quantitative findings in the biochemical sciences.

As a team scientist, Dr. Schnell’s research interest is to investigate complex biomedical systems comprising many interacting components, where modeling and theory may aid in the identification of the key mechanisms underlying the behavior of the system as a whole. His collaborators are primarily basic scientists who focus on the identification of molecular, biochemical or developmental mechanisms associated with diseases. To this end, Dr. Schnell’s expertise plays a central role in the identification of these mechanisms. Using mathematical and computational models, Dr. Schnell can formulate several hypothetical model mechanisms in parallel, which are compared with independent experimental data used to construct the models. The resulting comparisons are then independent between models, and any models that satisfy statistical measures of similarity will be used to make predictions, which will be tested experimentally by his collaborators. The model validated by the experiments will be considered the mechanism capable of explaining the behavior of the systems.