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# Development of a Comparative Genomics-Driven Knowledge Graph Framework for Translational Research

Baptiste Imbert, Jonathan Kreplak, Nadim Tayeh

► To cite this version:

Baptiste Imbert, Jonathan Kreplak, Nadim Tayeh. Development of a Comparative Genomics-Driven Knowledge Graph Framework for Translational Research. Plant & Animal Genome Conference (PAG), Comparative Genomics Workshop, Jan 2024, San Diego (CA), United States. http://05249622

HAL Id: hal-05249622

https://hal.inrae.fr/hal-05249622v1

Submitted on 11 Sep 2025

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Distributed under a Creative Commons Attribution 4.0 International License
# Development of a Comparative Genomics-Driven Knowledge Graph Framework for Translational Research

## Comparative Genomics

Baptiste Imbert
3rd year PhD student

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# Pulses have strong agronomic and nutritional assets

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- nitrogen source for next crops

- diversification crops in rotations

## Agronomy

### Seed composition

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- high protein content

- high starch content

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### Food

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### Globally consumed

- 11 main crop species used worldwide

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Semba et al., Global Food Security, 2021

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### Feed

## Nutrition
# Pulse yields are unstable, partly due to multiple (a)biotic stresses

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Abiotic stresses:
**drought/
frost**

Pathogens:
**root rot**
*(Aphanomyces)*

Pests:
**bruchids**

* Fluctuating yields and susceptibility to multiple stresses contribute to a lower area devoted to legumes

* More tolerant varieties are needed as climate change intensifies
# Subfamily Papilionoideae includes many widely used, phylogenetically close crops

* Pulses include a high number of species, usually clustered in 2 groups:

* cool-season legumes (Galegoids)

* lentil

* faba bean

* pea

* chickpea

* warm-season legumes (Milletioids)

* soybean

* mung bean

* All these species arised from a common ancestor ~ 55 MYA

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Whole genome duplication

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Whole genome triplication

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Prunus persica

Populus trichocarpa

Arabidopsis thaliana

adapted from Kreplak et al., *Nature Genetics*, 2019

Fabeae

Trifoliateae

Cicereae

Loteae

Phaseoleae

Genist.

Dalberg.
# Cross-species knowledge transfer can be a key driver for crop improvement

* Omic and genetic data have been unevenly generated in legumes

* Can we use information from one species to inform another?

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Orthology-focused comparative genomics is an
important tool for translational research

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# Orthology-focused comparative genomics is an important tool for translational research

<figure><img src="image_17.png" /></figure>

* Synteny in legume species is highly conserved

* Here, syntenic blocks are identified using **MCScanX** and orthogroups using **OrthoFinder**

* This method allows to get syntenic orthologs
# Orthology-focused comparative genomics is an important tool for translational research

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* Synteny in legume species is highly conserved

* Here, syntenic blocks are identified using **MCScanX** and orthogroups using **OrthoFinder**

* This method allows to get **syntenic orthologs**

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easier to pinpoint
**functional orthologs**
among homologs
# Orthology-focused comparative genomics is an important tool for translational research

<figure><img src="image_20.png" /></figure>

* Synteny in legume species is highly conserved

* Here, syntenic blocks are identified using **MCScanX** and orthogroups using **OrthoFinder**

* This method allows to get syntenic orthologs

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easier to pinpoint
**functional orthologs**
among homologs
# Ortho_KB is a new graph framework for translational research in plants

* Ortho_KB allows the integration of genetic and RNA-seq data for a selection of species

* Files produced can be imported in a Neo4j database

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The current version of Ortho_KB
includes up to 29 core
categories of nodes

gene_id: gene8

chr: chr3

start: 358

stop: 1465

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GRAPH DATABASE

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# The current version of Ortho_KB includes up to 29 core categories of nodes

gene_id: gene8

chr: chr3

start: 358

stop: 1465

neo4j

## GRAPH DATABASE

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Node

Relationship

- HAS_TRANSCRIPT

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RNA

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# The current version of Ortho_KB includes up to 29 core categories of nodes

gene_id: gene8

chr: chr3

start: 358

stop: 1465

neo4j

## GRAPH DATABASE

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Node

Relationship

HAS_TRANSCRIPT

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RNA

Node

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Genetics

Check the poster PE0696 for more info!

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The current version of Ortho_KB
includes up to 29 core
categories of nodes

gene_id: gene8

chr: chr3

start: 358

stop: 1465

neo4j

GRAPH DATABASE

<figure><img src="image_35.png" /><figcaption>Node</figcaption></figure>

<caption>Relationship</caption>

- HAS_TRANSCRIPT

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<figure><img src="image_37.png" /><figcaption>Node</figcaption></figure>

<figure><img src="image_38.png" /><figcaption>Genetics</figcaption></figure>

OrthoLegKB is an
instance of Ortho_KB
for legume species

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# Genetic loci associated to specific traits can be queried in OrthoLegKB for multiple species

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* All QTL in the database have physical positions on the genomes

* We can therefore compare genetic loci from different datasets on the same species

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yield trait

flowering trait

colocalizing QTL
of flowering time

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Query in
Cypher

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Pea chr3

Results from the development version
# Genetic loci associated to specific traits can be queried in OrthoLegKB for multiple species

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* All QTL in the database have physical positions on the genomes

* We can therefore compare genetic loci from different datasets on the same species

* Or genetic loci from different species located within **syntenic blocks**!

Results from the development version

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<figure><img src="image_49.png" /><figcaption>Faba bean chr5</figcaption></figure>

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<figure><img src="image_51.png" /><figcaption>Pea chr3</figcaption></figure>
# Expression of genes underlying the QTL, can be searched from all available organ/tissue samples

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# Expression of genes underlying the QTL, can be searched from all available organ/tissue samples

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1. Query genes within the confidence interval of the QTL

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# Expression of genes underlying the QTL, can be searched from all available organ/tissue samples

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1. Query genes within the confidence interval of the QTL

2. Keep genes annotated by GO:0048573 (photoperiodism, flowering)

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# Expression of genes underlying the QTL, can be searched from all available organ/tissue samples

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1. Query genes within the confidence interval of the QTL

2. Keep genes annotated by GO:0048573 (photoperiodism, flowering)

3. Get their expression in different tissues during the flowering stage

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# Expression of genes underlying the QTL, can be searched from all available organ/tissue samples

<figure><img src="image_61.png" /></figure>

1. Query genes within the confidence interval of the QTL

2. Keep genes annotated by GO:0048573 (photoperiodism, flowering)

3. Get their expression in different tissues during the flowering stage

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Expression of genes in the confidence interval are
available in different organs/tissues

* Out of the 11 genes selected under this QTL, 1 gene showed a strong expression at the *flowering stage* (Alves-Carvalho et al., The Plant Journal, 2015)

* *Psat.cameor.v2.3g170300* is strongly expressed in the *peduncle*, the *stem*, *leaves* and *tendrils*

* This gene is in fact the ortholog of the *FTa1* gene known for its role in flowering time

TPM

<figure><img src="image_63.png" /><figcaption>3 genes with almost no expression were excluded</figcaption></figure>
# Expression of genes in the confidence interval are available in different organs/tissues

* The ortholog of pea *FTa1* in faba bean is

*Vfaba.Hedin2.R1.5g087000*

* This gene also displays a preferential expression in the aerial part of the plant (vascular leaf and stem)

* These information support the hypothesis of **similar roles** for *FTa1* genes in pea and faba bean

* To investigate further...

TPM

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# Conclusions and perspectives

* We have created a comparative genomics framework for translational research: **Ortho_KB**

* The framework currently supports:

* functional annotations

* transcriptomic data

* genetic data

* Currently, its legume instance **OrthoLegKB** links reference genomes and associated data of 6 species, through orthology and synteny

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* Further adapt the Ortho_KB model to suit the needs of the community

* Integrate more datasets from the literature in OrthoLegKB

* Exploit the current content of the database!
Thank you for your attention

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Thanks to all the ECP team and
especially to:

* Nadim Tayeh (supervisor)

* Judith Burstin (co-supervisor)

* Jonathan Kreplak (bioinformatics engineer)

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RÉPUBLIQUE
FRANÇAISE

Liberté
Égalité
Présentité

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anr INRA©

CULTIVER
PROTÉGER
autrement

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SPECIFICS

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a special thanks to Vijay Tiwari and Nathan M.
Springer for letting me present my work here!
SUPPLEMENTARIES
<figure><img src="image_72.png" /><figcaption># Synteny among legume species</figcaption></figure>