A systems model of the rumen

Lead Research Organisation: Aberystwyth University
Department Name: IBERS

Abstract

The ruminant system converts fibrous feed of low nutritional value to a product of high nutritional value, via the actions of a symbiotic microbial population. Effectively it is a highly stable chemostat for microbial transformation of plant material into the volatile fatty acids and microbial cells that contribute directly to animal nutrition. The goal is to design forage substrates containing the correct balance of macro and micronutrients to promote effective fibre digestion and microbial proliferation whilst inhibiting methanogenic species. However, unlike the feed matching requirements of relatively simple industrial chemostatic systems, the requirements of the rumen in terms of species abundance and/or functionality to provide animal health and digestive efficiency is still incompletely understood, which to date has made it difficult to manipulate a priori. Furthermore, feed components can affect fermentation outputs but the mechanism underlying these effects is poorly described at the molecular level. In this sub-programme we will develop bioinformatic methodologies to enable examination of the whole rumen ecosystem in terms of the metagenomic, metatranscriptomic, proteomic and metabolomic datasets obtained from sub-programmes 2 and 3 and to inform in the construction of a systems/network model of the rumen. This resource will inform targeted rumen manipulation, either by development and use of appropriate feed additives or through selective plant breeding to incorporate key traits in forage to achieve improved production and/or quality targets.

Publications

10 25 50

 
Description The key aim of this work was to increase our understanding of the intra-species relationships in complex microbial communities, using the rumen as an example. Typically next generation sequencing data is used to describe the community in terms of abundance of microbiota at various classification levels. This work has developed and released to the public the custom computational tools needed for analysis of stable and changing communities. We have released software related to analysis of metagenomic data with particular reference to the Hungate 1000 data set, thereby reducing the number of identification errors. Importantly we have established and published procedures for network modelling of the rumen ecosystem established at genomic, transcriptomic, proteomic, and metabolomic levels. These tools have shown differential complexity of the interacting communities depending on location (attached to feed or planktonic) and give further depth to our understanding of successional colonisation of feed by clearly indicating changes in the complexity and relationships between interacting organisms at different stages of feed degradation.
Exploitation Route We have developed software which has been made freely available to the user (academic) community for use in rumen and other microbial ecosystems (eg soil, water, skin microbiomes).
Sectors Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software),Education,Environment

 
Description Chair in Rumen Systems Biology
Amount £600,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2013 
End 12/2017
 
Description Climate KIC RuMeClean
Amount £218,042 (GBP)
Organisation BioHorizons 
Sector Private
Country United States
Start 01/2014 
End 12/2015
 
Description FACCEJPI Rumenstability
Amount £25,200 (GBP)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 02/2014 
End 01/2017
 
Description GCRF-IAA
Amount £300,000 (GBP)
Funding ID BB/GCRF-IAA/09 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 03/2017
 
Description Global Challenges Research Fund Data and Resources
Amount £942,900 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2016 
End 07/2017
 
Description International Partnering Award Brazil
Amount £41,531 (GBP)
Funding ID BB/L026716/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2014 
End 03/2018
 
Description KESS studentship
Amount £56,000 (GBP)
Organisation European Social Fund (Welsh Government/ EU) 
Sector Public
Country United Kingdom
Start 10/2016 
End 09/2019
 
Description Marie Curie, Toxin sequestration in frogs
Amount £7,036 (GBP)
Organisation Irish Research Council 
Sector Public
Country Ireland
Start 10/2014 
End 09/2017
 
Description NRN antimicrobials from bovine metagenomes
Amount £49,970 (GBP)
Organisation National Research Network, Life Sciences and Health 
Sector Public
Country United Kingdom
Start 10/2014 
End 09/2015
 
Description Postgraduate studentship Sam Nicholls
Amount £53,500 (GBP)
Organisation University of Wales 
Department Institute of Biological Environmental and Rural Sciences (IBERS)
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 09/2017
 
Description TSB beef supply chain
Amount £386,672 (GBP)
Funding ID 101407 
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 02/2013 
End 02/2016
 
Description Teagasc ruminant methane
Amount £72,728 (GBP)
Organisation Teagasc 
Department Teagasc Food Research Centre
Sector Academic/University
Country Ireland
Start 01/2014 
End 01/2018
 
Description WG Land use review
Amount £13,000 (GBP)
Organisation Welsh Assembly 
Sector Public
Country United Kingdom
Start 03/2014 
End 07/2014
 
Description BBSRC UK-Brazil Partnering Award 
Organisation Federal University of Minas Gerais
Country Brazil 
Sector Academic/University 
PI Contribution Members of research team have travelled to Brazil to share knowledge of characterising and exploiting novel antimicrobials within the rumen microbiola
Collaborator Contribution Members of the receiving organisation in Brazil hosted the visit and shared in their understanding of exploiting novel antimicrobials within the rumen microbiola
Impact Knowledge sharing
Start Year 2014
 
Title Clan_Check 
Description This is designed for large-scale phylogenomic analyses where the user may have thousands of phylogenetic trees. While every effort may have been taken to ensure that the best orthlogs have been chosen, sometimes due to hidden paralogy it is not easy to get the choice right. In these cases, the only evidence that the gene family may be problematic is when the resulting phylogeentic tree is "incorrect". One way to test for "problematic" gene families is to look for "incontrovertible relationships" that are not part of the question being asked in the study, but without doubt should exist if the taxa are in the tree. An example of this is, if I was carrying out a phylogenomic study of the fishes and used several mammals as an outgroup, then I should never expect the mammal clan to be paraphyletic [edit - whats the equivalent of paraphyly for a clan?]. In this case the mammals are an incontrovertible clan. If the mammals are paraphyletic with the fishes, then it is very likely that one of the internal branches of the tree represents a duplication and not a speciation event, and so they are not all orthologs. Clan_check searches for these instances. If given many such clans to check, researchers can assess the number of these clans that are violated and decide on the weight of evidence necessary to remove or re-visit the analysis of that gene family. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Program to check trees for compatibility with defined monophyletic [edit - not right terminology ] groups - "The incontrovertible clan test" 
URL https://github.com/ChrisCreevey/clan_check
 
Title Clann 
Description To construct supertrees and explore the underlying phylogenomic information from partially overlapping datasets. The program Clann has been developed to provide implementations of several supertree methods. The methods implemented all allow the investigation of data in a phylogenomic context. It is important that the user understands the advantages and limitations of these methods. It is also important for the user to know that the software is designed to perform a number of different tasks, however the interpretation of the results is left entirely to the user. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Improved methodology to implement methods of determining the optimal phylogenetic supertrees, given a set of input source trees. 
URL https://github.com/ChrisCreevey/clann
 
Title Gretel 
Description Gretel is a Python package providing a command line tool for the recovery of haplotypes from metagenomic data sets. Gretel parses an alignment of reads into a Hansel matrix and uses the evidence of SNP pairs observed to appear on the same reads to probabilistically reconstruct the most likely haplotypes. Gretel uses an L'th order Markov chain model to reconstruct likely sequences of variants that constitute haplotypes in the real metagenome. Our approach involves graph-like traversal of the data within the Hansel matrix. Edges are probabilitically weighted based on the evidence on the reads, as well as the haplotype as it has been reconstructed so far. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Gretel is designed to recover haplotypes from your data set, without the need for setting (or optimisation) of any parameters. Gretel does not require a priori knowledge of your input data (such as its contents, or the true number of haplotypes) and makes no assumptions regarding the distributions of alleles at variant sites and uses the available evidence from the aligned reads without altering or discarding the observed varations. Gretel is the first tool capable of recovering haplotypes from metagenomes. Whilst tools exist for analogous haplotyping problems, such as the assembly of viral quasispecies, typically these tools rely on overlap approaches that create too many unranked haplotypes. Gretel is capable of ranking the haplotypes it outputs by their likelihood. Gretel requires no parameters and our approach is robust to sequencing error and misalignment noise. 
URL https://github.com/SamStudio8/gretel
 
Title Hansel 
Description Hansel is a probabilistically-weighted, graph-inspired, novel data structure. Hansel is designed to store the number of observed occurrences of a symbol a appearing at some position in space or time i, co-occurring with another symbol b at another position in space or time j. One may traverse along ordered positions in time or space, each time predicting the next most likely symbol of the sequence to traverse to, given the previously selected symbols in the path. Hansel presents a user-friendly API for managing and interacting with the data stored within. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Hansel and Gretel are distributed under the MIT license, see LICENSE 
URL https://github.com/samstudio8/hansel
 
Title MGKIT: Toolkit for metagenomic data analysis; latest update 21.2.2017 
Description The aim of this library is to provide a series of useful modules and packages to make it easier to build custom pipelines for metagenomics or any kind of bioinformatics analysis. It integrates other well known python libraries in bioinformatics, like HTSeq, pysam, numpy and scipy. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact A tutorial pipeline is provided in the Documentation. A discussion mailing list is available at mgkit-users. 
URL https://bitbucket.org/setsuna80/mgkit
 
Title MGkit: Metagenomic Framework for the study of Microbial Communities 
Description INTRODUCTION: While metagenomics has been used extensively to study microbial communities from a taxonomic and functional perspective, little has been done to address how the species in a microbiome are adapted to and maintain specific roles in dynamic environments like the rumen. RATIONALE: To address this issue we have developed a framework for the robust analysis of metagenomic data that includes fully automated analysis from next-generation sequencing (NGS) reads to assembly, gene-predicition and taxonomic identification. Furthermore we imple- ment approaches to estimate SNP diversity in metagenomic samples and carry out statistical tests to identify genes where sequence diver- sity exists. The framework allows easy customisation of any metagenomic workflow, by providing the necessary functions and scripts to manipulate data from NGS pipelines and provides bespoke analyses of the data. MGKit also does not enforce a specific pipeline on the user, but leverages analysis patterns and common files formats (Fig. 1) to make it easier to experiment with different types of analyses. MGKit is implemented in Python and uses common libraries used in the Python Scientific Community, like NumPy, SciPy, Matplotlib and pandas, along with packages used in NGS data analysis, like HTSeq and pysam. OPEN SOURCE LICENCE: GPL and free for academic use 
Type Of Technology Software 
Year Produced 2012 
Open Source License? Yes  
Impact Discussion mailing list available at mgkit-users. 
URL https://bitbucket.org/setsuna80/mgkit
 
Title Machete 
Description Bootstrap proportion (BP) support remains a commonly used metric of the reliability of genome-scale phylogenetic analyses because sampling error decreases as the length of sequences increase resulting in a trend where BP support approaches 100%. However, not all conflicting phylogenetic signal is due to sampling error; processes such as incomplete lineage sorting and horizontal gene transfer can result in valid alternative genetic histories. Despite this, with long-enough alignments, 100% BP can be achieved even if 49% of the data supports an alternative topology. The heterogeneous nature of the underlying support for branches with 100% BP requires a novel approach and a change in our notion of "support". To address this, Machete implements a likelihood decay support value. Based on the premise of Bremmer support, it is the difference in likelihoods of the optimal trees that do or do not include a given split. Likelihood decay represents a novel way to assess support which discriminates between different internal branches and is insensitive to alignment length. Machete takes as input a nexus formatted aligned DNA or Amino Acid sequences and uses PAUP to calculate the likelihood decay supports for each internal branch of the resulting tree. Machete controls and interacts with Paup using a pipe, and not using a predefined script. This allows dataset-specific optimisations to be carried out (as a user would). 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Improved boot-strapping. 
URL https://github.com/ChrisCreevey/machete
 
Title Spherical metagenomic assembly software: latest version updated 7.2.2017 
Description Spherical is an iterative approach to assembling metagenomic datasets. Spherical has been designed to produce a more complete assembly from deep sequenced metagenomic data. Utilization of multiple iterations of assembly allows for regions which otherwise would be missed to be assembled without a reduction in contig accuracy. Another use for Spherical is its ability to produce metagenomic assemblies using a subset of the initial input file, allowing for assembly of a metagenome whilst using a fraction of the RAM that would otherwise be required. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Open source metagenomic assembler suitable for use in multiple ecosystems. 
URL https://github.com/thh32/Spherical
 
Description "Y Bol Buwch" (All Things Rumen) exhibit at Royal Welsh Show, July 2015 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact • Initiated and oversaw "Y Bol Buwch" (All Things Rumen) exhibit at Royal Welsh Show, July 2015 including "Live lab" deonstrations of DNA extraction and fermentation and "Bug bashing" (type of coconut shy).
Year(s) Of Engagement Activity 2015
 
Description AKS Invited to give seminar at Oxford Brookes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact Talked to a group of bioscience postgraduates and supervisors. Wide ranging discussions on practicalities and ethics associated with livestock and the environment. New potential research contacts made.
Year(s) Of Engagement Activity 2017
 
Description Public engagement (Royal Welsh Show) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Demonstration of interactive rumen over four days of national agricultural show, leading to discussion with members of the public and prospective students.
Year(s) Of Engagement Activity 2016
 
Description Sparking Impact Meeting - Waitrose Supply Chain/IBERS 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact With British producers facing ever-increasing expectations - to deliver traceability, meet higher environmental standards and maintain the countryside - Waitrose, IBERS and suppliers have been working together to share experiences on topics such as animal and plant diseases, food security issues and strains on productivity. This event gave suppliers, large and small, direct access to Waitrose buyers, food technologists and scientists and helped smaller producers, in particular, to understand food legislation.

The outcome of the event was a sharing of best practice throughout Waitrose's supply chain and beyond.
Year(s) Of Engagement Activity 2013
 
Description Visit to WHEB, EU, Brussels 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Visit of 7 researchers to Welsh Higher Education Brussels, organised by National Research network (Wales) in Low Carbon Energy and Environment. Objective was to engage with Research Programme Directors and managers of platforms related to agriculture.
Year(s) Of Engagement Activity 2016
 
Description information for SoB poster 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Dr Kingston-Smith collaborated with Society of Biology during their preparation of a poster for schools titled "What goes in to a cow?" aimed at GCSE level students.

Posters used by Society of Biology Staff during National Science week. Posters available to schools.
Year(s) Of Engagement Activity 2013