Diana Lin

Diana Lin

Research Programmer - Data Scientist at Canada's Michael Smith Genome Sciences Centre @ BC Cancer

Publications

You can also find my articles on my Google Scholar profile.

Associating Biological Activity and Predicted Structure of Antimicrobial Peptides from Amphibians and Insects

Published in Antibiotics, 2022

Abstract: Antimicrobial peptides (AMPs) are a diverse class of short, often cationic biological molecules that present promising opportunities in the development of new therapeutics to combat antimicrobial resistance. Newly developed in silico methods offer the ability to rapidly discover numerous novel AMPs with a variety of physiochemical properties. Herein, using the rAMPage AMP discovery pipeline, we bioinformatically identified 51 AMP candidates from amphibia and insect RNA-seq data and present their in-depth characterization. The studied AMPs demonstrate activity against a panel of bacterial pathogens and have undetected or low toxicity to red blood cells and human cultured cells. Amino acid sequence analysis revealed that 30 of these bioactive peptides belong to either the Brevinin-1, Brevinin-2, Nigrocin-2, or Apidaecin AMP families. Prediction of three-dimensional structures using ColabFold indicated an association between peptides predicted to adopt a helical structure and broad-spectrum antibacterial activity against the Gram-negative and Gram-positive species tested in our panel. These findings highlight the utility of associating the diverse sequences of novel AMPs with their estimated peptide structures in categorizing AMPs and predicting their antimicrobial activity.

Recommended citation: Richter, A., Sutherland, D., Ebrahimikondori, H., Babock, A., Louie, N., Li, C., Coombe, L., Lin, D., Warren, R.L., Yanai, A., Kotkoff, M., Helbing, C.C., Hof, F., Hoang, L.M.N., & Birol, I. (2022). "Associating Biological Activity and Predicted Structure of Antimicrobial Peptides from Amphibians and Insects." Antibiotics 11(12):1710. https://doi.org/10.3390/antibiotics11121710

Mining Amphibian and Insect Transcriptomes for Antimicrobial Peptide Sequences with rAMPage

Published in Antibiotics, 2022

Abstract: Antibiotic resistance is a global health crisis increasing in prevalence every day. To combat this crisis, alternative antimicrobial therapeutics are urgently needed. Antimicrobial peptides (AMPs), a family of short defense proteins, are produced naturally by all organisms and hold great potential as effective alternatives to small molecule antibiotics. Here, we present rAMPage, a scalable bioinformatics discovery platform for identifying AMP sequences from RNA sequencing (RNA-seq) datasets. In our study, we demonstrate the utility and scalability of rAMPage, running it on 84 publicly available RNA-seq datasets from 75 amphibian and insect species—species known to have rich AMP repertoires. Across these datasets, we identified 1137 putative AMPs, 1024 of which were deemed novel by a homology search in cataloged AMPs in public databases. We selected 21 peptide sequences from this set for antimicrobial susceptibility testing against Escherichia coli and Staphylococcus aureus and observed that seven of them have high antimicrobial activity. Our study illustrates how in silico methods such as rAMPage can enable the fast and efficient discovery of novel antimicrobial peptides as an effective first step in the strenuous process of antimicrobial drug development.

Recommended citation: Lin, D., Sutherland, D., Aninta, S.I., Louie, N., Nip, K.M., Li, C., Yanai, A., Coombe, L., Warren, R.L., Helbing, C.C., Hoang, L.M.N., & Birol, I. (2022). "Mining Amphibian and Insect Transcriptomes for Antimicrobial Peptide Sequences with rAMPage." Antibiotics 11(7):952. https://doi.org/10.3390/antibiotics11070952

The genome of the forest insect pest Pissodes strobi reveals genome expansion and evidence of a Wolbachia endosymbiont

Published in G3 Genes | Genomes | Genetics, 2022

Recommended citation: Gagalova, K. K., Whitehill, J. G. A., Culibrk, L., Lin, D., Levesque-Tremblay, V., Keeling, C. I., Coombe, L., Birol, I., Bohlmann, J., Jones, S. J. M. (2022). "The genome of the forest insect pest Pissodes strobi reveals genome expansion and evidence of a Wolbachia endosymbiont." G3 Genes|Genomes|Genetics, jkac038. https://doi.org/10.1093/g3journal/jkac038

High throughput in silico discovery of antimicrobial peptides in amphibian and insect transcriptomes

Published in University of British Columbia, 2020

Abstract: Antimicrobial peptides (AMPs) are a family of short defence proteins produced naturally by all multicellular organisms, varying from microorganisms to humans. Since resistance to AMPs is less frequent as to antibiotics, they may serve as a potential alternative. Past research has shown that amphibians have the richest known AMP diversity, specifically the North American bullfrog has demonstrated potential in aiding the discovery of novel putative AMPs. Antibiotic resistance is becoming more prevalent each day, requiring agricultural practices to reduce the use of antibiotics to protect human health, animal health, and food safety. To reduce the use of antibiotics, the goal of my thesis is to develop and execute an AMP discovery pipeline to discover AMPs suitable for pharmaceutical development. In this thesis, I have accomplished rAMPage: Rapid Antimicrobial Peptide Annotation and Gene Estimation. rAMPage is a scalable, high throughput bioinformatics-based discovery platform for mining AMP sequences in publicly available genomic resources. RNA-seq amphibian and insect reads from the Sequence Read Archive (SRA) are used. After trimming, reads are assembled with RNA-Bloom into transcripts, filtered, and translated in silico. Then, the translated protein sequences are compared to known AMP sequences from the NCBI protein database and specific AMP databases APD3 and DADP, via homology search. These sequences are cleaved into their mature/bioactive form. Next, machine learning algorithm AMPlify is employed to classify and prioritize the candidate AMPs based on their AMP probability score. Finally, these candidate AMPs are annotated and characterized. Across 84 datasets, rAMPage detected > 1,000 putative AMPs, where 90 sequences have been selected for downstream validation.

Recommended citation: Lin, D. (2021). "High throughput in silico discovery of antimicrobial peptides in amphibian and insect transcriptomes." University of British Columbia. https://dx.doi.org/10.14288/1.0402476

Complete Chloroplast Genome Sequence of a Black Spruce (Picea mariana) from Eastern Canada

Published in Microbiology Resource Announcements, 2020

Abstract: Here, we present the chloroplast genome sequence of black spruce (Picea mariana), a conifer widely distributed throughout North American boreal forests. This complete and annotated chloroplast sequence is 123,961 bp long and will contribute to future studies on the genetic basis of evolutionary change in spruce and adaptation in conifers.

Recommended citation: Lo, T., Coombe, L., Lin, D., Warren, R. L., Kirk, H., Pandoh, P., Zhao, Y., Moore, R. A., Mungall, A. J., Ritland, C., Bousquet, J., Jones, S. J. M., Bohlmann, J., Thomson, A., & Birol, I. (2020). "Complete Chloroplast Genome Sequence of a Black Spruce (Picea mariana) from Eastern Canada." Microbiology Resource Announcements, 9(39). https://doi.org/10.1128/MRA.00877-20

Complete Chloroplast Genome Sequence of an Engelmann Spruce (Picea engelmannii, Genotype Se404-851) from Western Canada

Published in Microbiology Resource Announcements, 2019

Abstract: Engelmann spruce (Picea engelmannii) is a conifer found primarily on the west coast of North America. Here, we present the complete chloroplast genome sequence of Picea engelmannii genotype Se404-851. This chloroplast sequence will benefit future conifer genomic research and contribute resources to further species conservation efforts.

Recommended citation: Lin, D., Coombe, L., Jackman, S. D., Gagalova, K. K., Warren, R. L., Hammond, S. A., McDonald, H., Kirk, H., Pandoh, P., Zhao, Y., Moore, R. A., Mungall, A. J., Ritland, C., Doerksen, T., Jaquish, B., Bousquet, J., Jones, S. J. M., Bohlmann, J., & Birol, I. (2019). "Complete Chloroplast Genome Sequence of an Engelmann Spruce (Picea engelmannii, Genotype Se404-851) from Western Canada." Microbiology Resource Announcements, 8(24). http://doi.org/10.1128/MRA.00382-19

Complete Chloroplast Genome Sequence of a White Spruce (Picea glauca, Genotype WS77111) from Eastern Canada

Published in Microbiology Resource Announcements, 2019

Abstract: Here, we present the complete chloroplast genome sequence of white spruce (Picea glauca, genotype WS77111), a coniferous tree widespread in the boreal forests of North America. This sequence contributes to genomic and phylogenetic analyses of the Picea genus that are part of ongoing research to understand their adaptation to environmental stress.

Recommended citation: Lin, D., Coombe, L., Jackman, S. D., Gagalova, K. K., Warren, R. L., Hammond, S. A., Kirk, H., Pandoh, P., Zhao, Y., Moore, R. A., Mungall, A. J., Ritland, C., Jaquish, B., Isabel, N., Bousquet, J., Jones, S. J. M., Bohlmann, J., & Birol, I. (2019). "Complete Chloroplast Genome Sequence of a White Spruce (Picea glauca, Genotype WS77111) from Eastern Canada." Microbiology Resource Announcements, 8(23). https://doi.org/10.1128/MRA.00381-19