David S. Wishart

Wishart's research interests span a number of areas including structural biology, computational biology, bioinformatics, nanobiology, metabolomics, nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry. A common theme to his research career has been the development of techniques, technology cores, protocols, data resources or computer programs that make science simpler, faster, cheaper or easier.^[1][2][3]

Wishart began his research career in the field of protein NMR in the early 1990s, focusing on using NMR spectroscopy to characterize protein structure and protein denaturation. At the time, protein structural analysis by NMR required hundreds of hours of manual data analysis and data tabulation. In an effort to accelerate the process, Wishart discovered a trend with regard to how the NMR chemical shifts of amino acid residues changed systematically with regard to their secondary structure. He proceeded to develop a technique, called the chemical shift index, also known as CSI, that used a set of simple rules and simple chemical shift tables that allowed scientists to directly use protein chemical shift assignments to rapidly determine the type and location of protein secondary structures in proteins in just seconds.^[14][15] Subsequently, Wishart showed how NMR chemical shifts could be used to easily and rapidly measure protein flexibility via the random coil index or RCI.^[16][17] Later, he showed how it was possible to use chemical shifts to determine protein backbone torsion angles with a program called PREDITOR.^[18] Wishart also determined how chemical shifts could be used to measure residue accessible surface area,^[19] and to identify super secondary structure elements.^[19][20] To further extend this work, Wishart developed innovative methods to determine the 3D structure of proteins using a technique called chemical shift threading with programs such as GeNMR, CS23D and E-Thrifty.^[21][22][23] To help compare and assess existing protein NMR structures, Wishart also developed methods to accurately predict protein chemical shifts from 3D coordinates using programs such as ShiftX and ShiftX2.^[24][25] At the same time he also developed methods to re-reference incorrectly assigned protein chemical shifts using programs such as SHIFTCOR and PANAV.^[26] These programs were used to help create protein NMR databases such as RefDB that contain 1000s of re-referenced chemical shifts.^[27] Wishart's papers describing these NMR methods have been cited more than 15,000 times and are now considered^{[by whom?]} to be foundational techniques for much of modern protein NMR.

In the early 2000s, Wishart turned his attention from looking at big molecules such as proteins to looking at small molecules (metabolites). In 2001 he developed and then patented NMR-based techniques (leading to the spin-off company Chenomx^[5]) that permitted the rapid identification and quantification of metabolites by NMR in biofluids.^[28] In 2005, he conceived of the Human Metabolome Project (HMP) ^[29] – the metabolomic equivalent of the Human Genome Project. Wishart raised over $10 million in funding from Genome Canada and launched a multi-institutional, pan-Canadian program to systematically identify all metabolites, drugs and xenobiotics in clinically important human biofluids. The goal of HMP is to provide the scientific community with easily accessible reference data about human metabolites, thereby making metabolomic data analysis more comprehensive and much simpler. As of 2022^[update], the HMP is still ongoing and has led to the identification of more than 240,000 human metabolites, 6000 drugs and drug metabolites, 70,000 food constituents and 3000 toxins and contaminants.^[30][31][32] This information, along with many tools to facilitate metabolite identification and interpretation, have been archived in several publicly available databases created by the Wishart lab. These include the Human Metabolome Database (HMDB), which contains data on human metabolites and their structures, along with descriptions, NMR spectra and MS spectra.^[33] Another resource developed from the project is DrugBank,^[31] a database of all known, approved drugs and their target molecules. Other databases developed by the Wishart lab include FooDB,^[32] a database of food constituents and food additives; and T3DB,^[34] a database of toxic compounds and contaminants as well as their toxicological effects.

In 2011, Wishart founded The Metabolomics Innovation Centre (TMIC) and served as its first director (2011-2019).^[35] Wishart's laboratory within TMIC houses over $8 million in modern LC-MS, GC-MS and NMR equipment. His lab routinely processes more than 20,000 samples each year. Using this wide array of equipment, Wishart helped develop a number of quantitative metabolomics techniques for NMR ^[36][37] and liquid chromatography mass spectrometry.^[38][39]  Using these methods, Wishart and his team have conducted comprehensive, quantitative metabolome analyses of human serum,^[40] urine,^[41] saliva,^[42] cerebrospinal fluid ^[43] and feces.^[44]

Wishart has made all his lab's data resources, computer programs, algorithms and techniques publicly accessible. This open science/open access initiative has been aimed at providing tools and techniques to make biomolecular NMR, metabolomics, structural biology and a number of related techniques more accessible for all scientists. So far, this initiative has led Wishart's lab to develop and release more than 100 publicly accessible web servers and web-based databases,^[45] including NP-MRD^[46] and CFM-ID.^[47] To further his open-science efforts, Wishart co-founded several educational bioinformatics programs such as the Canadian Bioinformatics Workshops and has been actively involved in other international standardization and open-source initiatives to make computational biology resources more widely available and accessible.

Wishart is married to Debby Waldman, a freelance writer and editor from Utica, New York. He has two children: Elizabeth, an epidemiologist; and Noah, a civil engineer. They all live and work in Edmonton, Alberta.^[48]