Research

Methods to detect hidden diversity

Develop, test, and refine new computational tools and technologies to uncover hidden aspects of biodiversity.

Project Summary.

Funding:

This research is supported by the UKRI Biotechnology and Biological Sciences Research Council (BBSRC).

Earlham Institute Strategic Programme Grant Decoding Biodiversity BBX011089/1 and its constituent work package BBS/E/ER/230002A.

Harnessing the Earth's biodiversity is a strategic challenge that is increasingly urgent due to global biodiversity decline.

Compounding the issue is the scale and complexity of biological information, which has made modern bioscience a data-intensive discipline.

In recent years, new long read sequencing technologies have led to an explosion in the number of reference quality genomes and enabled reconstruction of bacterial genomes from metagenomes.

As part of our Decoding Biodiversity Strategic Programme, we are testing and refining new computational tools and technologies to allow us to uncover hidden aspects of biodiversity.

Our work focuses on four key areas:

Construction of pangenomes
Optimising genome annotation through multi-omics integration
Methods to resolve functional roles in microbiomes
Microbial community dynamics in real time

Detail

Details.

Pangenome Construction

We are developing workflows to enable the haplotype-specific analysis of large, complex plant and fish genomes. Specifically, we are implementing pangenome graphs to identify and visualise genome rearrangements, and statistical methods to identify introgressions and sources of introgressed materials.

Working with our industrial partner, IBM Research, we will develop powerful, deployable, and scalable approaches for the detection of macro- and micro-structural changes in both prokaryotes and eukaryotes.

Additionally, we are developing new wet-lab techniques and algorithms to resolve strain-level genomes from complex microbial communities.

Genome annotation through multi-omics integration

The translational value of any genome assembly depends heavily on the quality of its annotation.

Led by the Core Bioinformatics Group, we are developing improved workflows and pipelines to ensure uniform gene structure annotations across diverse clades, subspecies, and haplotypes. Our novel pipelines are improving annotations of functional noncoding and coding sequences for non-model species.

Made available through our National Bioscience Research Infrastructure in Transformative Genomics, these tools will enable a greater understanding of the consequences of genetic variation, unlocking the full potential of genomes emerging from large scale initiatives such as the Earth Biogenome Project.

Resolving functional roles in microbiomes

We are developing methods to determine the functional role of individual taxa within a microbial community using a combination of novel experimental and computational techniques.

This work will model how different microorganisms function and interact within diverse microbial communities. Utilising expertise from across the Earlham Institute and Quadram Institute, we will improve our understanding of microbes' functional roles through defining pangenomes and transcriptomes.

Developing tools for in situ and selective sequencing

Nanopore technology presents an opportunity to deploy sequencing as a sensor, enabling in situ characterisation of environmental communities.

This offers the potential to monitor community dynamics in real-time, study the effect of interventions, and overcome difficulties with storage and transport of challenging samples.

However, to realise the potential of studying communities in situ, there is a need for new sampling protocols along with new analytical approaches that do not rely on high bandwidth internet connections or high-performance computing infrastructures.

The Earlham Institute has a strong history of developing such analysis tools, including NanoOK RT for real-time diagnostics, and MARTi (Metagenomic Analysis in Real-Time).

As a part of Decoding Biodiversity, we will extend MARTi to allow it to be used as an automated analysis solution for almost any in situ experiment.

Tools and data

Collaborators

Impact statement.

The scale and complexity of biological data has made bioscience a data-intensive discipline.

The Earlham Institute fits in the scientific ecosystem at the interface between data science and biology, providing an interdisciplinary research environment to deploy transformative technologies to generate and analyse data at scale, in order to address fundamental biological questions.

We are developing new tools to exploit the large-scale genomic and metagenomic collections and link them with the other forms of digital data.

This will allow us to both understand the evolutionary and ecological processes that have generated this diversity and, by better determining its functional significance in agriculture and biotechnology, address challenges posed by climate change.