BoMiProt: A database of bovine milk proteins

Highlights

• First bovine milk proteome database.

• Manual curation of over 3100 bovine milk proteins.

• Over 390 proteins were enriched with information from published literature.

• Protein entries were categorized based on whey, fat globule membrane & exosomes.

Abstract

Bovine milk has become an important biological fluid for proteomic research due to its nutritional and immunological benefits. To date, over 300 publications have reported changes in bovine milk protein composition based on seasons, lactation stages, breeds, health status and milk fractions while there are no reports on consolidation or overlap of data between studies. Thus, we have developed a literature-based, manually curated open online database of bovine milk proteome, BoMiProt (http://bomiprot.org), with over 3100 proteins from whey, fat globule membranes and exosomes. Each entry in the database is thoroughly cross-referenced including 397 proteins with well-defined information on protein function, biochemical properties, post-translational modifications and significance in milk from different publications. Of 397 proteins, over 199 have been reported with a structural gallery of homology models and crystal structures in the database. The proteome data can be retrieved using several search parameters such as protein name, accession IDs, FASTA sequence. Furthermore, the proteome data can be filtered based on milk fractions, post-translational modifications and/or structures. Taken together, BoMiProt represents an extensive compilation of bovine milk proteins from literature, providing a foundation for future studies to identify specific milk proteins which may be linked to mammary gland pathophysiology.

Biological significance

Protein data identified from different previously published proteomic studies on bovine milk samples (21 publications) were gathered in the BoMiProt database. Unification of the identified proteins will give researchers an initial reference database on bovine milk proteome to understand the complexities of milk as a biological fluid. BoMiProt has a user-friendly interface with several useful features, including different search criteria for primary and secondary information of proteins along with cross-references to external databases. The database will provide insights into the existing literature and possible future directions to investigate further and improve the beneficial effects of bovine milk components and dairy products on human health.

Introduction

Milk produced in the mammary gland contains a large and diverse set of proteins, fats, carbohydrates and bioactive substances which vary in abundance across stages of lactation, age and health status of the animal [[1], [2], [3]]. Recent comprehensive studies using mass spectrometry (MS) have collectively reported over 3100 proteins in bovine milk, suggesting that it has the complexity to serve as a biological fluid for identification of cellular, molecular and chemical changes indicative of mammary gland pathophysiology [1,2,[4], [5], [6], [7]]. Thus, a better understanding of the bovine milk proteome will not only enable us to improve animal health and well-being through appropriate veterinary and husbandry practices but also help improve different dairy products (e.g., cheese, yogurt, butter) for the betterment of human health.

In the post-genomic era, MS has been a very useful analytical tool to investigate different milk fractions such as whey, milk fat globule membrane (MFGM) and exosomes [6] for nutraceutical value [8,9]. More recently, improvements in the sensitivity of MS to an unprecedented scale have significantly contributed to the investigative studies on the changes in protein abundance and milk composition due to endogenous (e.g., breeds & lactation stages) and exogenous (e.g., seasons) factors [1,2,4], and diseases [10].

According to the United Nations Food and Agriculture Organization, cow milk contributes to 82% of world milk production, followed by buffalo milk at 14% (Food and Agriculture Organization. Gateway to dairy production and products, 2017; http://www.fao.org/dairy-production-products/production/dairy-animals/en/.). A significant number of bovine milk proteins, derivatives or bioactive peptides have been experimentally identified with considerable health benefits [11] including anti-carcinogenic (e.g., β-lactoglobulin, lactoferrin, α-lactalbumin) [12], anti-hypertensive (e.g. α-lactorphin, β-lactorphin, β-lactosin B and Casein-derived lactotripeptides) [13] and immunomodulatory (e.g. lactoferrin, lactoperoxidase, milk growth factor, immunoglobulin G) [14] properties. Although there is a continuous growing interest in research carried out by different groups in this field, the majority of the studies are “stand-alone” investigations with no efforts being made to consolidate prior data and/or report the degree of overlap with previously published literature. Recently, a comprehensive collection of the known chemical composition of bovine milk was reported in Milk Composition Database (MCDB) [15] and bovine milk proteome atlas, identifying potential indicators of negative energy balance in high producing dairy cows [3]. Nevertheless, there is no specialized resource of bovine milk proteome that would provide comprehensive information complementing the ongoing efforts of protein annotation as done in Swiss-Prot [16] and dbPTM. The dbPTM is a database for protein post-translational modifications (PTMs), which integrates experimentally validated information on parameters such as functions and/or PTMs [17]. Thus, to consolidate the existing information, data mining is imperative to collect and curate bovine milk proteome, given its economic and nutritional importance.

Given the necessity and a significant rise of interest in bovine milk, we have developed a bovine milk proteome database (BoMiProt) as a manually curated, comprehensive repository of published information on bovine milk proteins. In this database, over 3100 proteins have been included with primary information, 397 of which are provided with detailed protein annotations including protein function, biochemical properties, site-specific PTMs, functional role, the significance of the protein in milk, structural information and endogenous peptides. These well-annotated proteins with secondary information are called as ‘BoMiProt defined proteins’ in the database. Our report is a focused beginning of an effort to collect and curate publicly available voluminous bovine milk proteomics data and update the same in real-time when relevant literature is published or obtained. Collectively, BoMiProt is an in-depth bovine milk proteome reference database that provides a bird's eye view of the on-going research on bovine milk and possible information gaps that need attention for maximizing health-promoting effects of milk and different dairy products.