era7 bioinformatics and_the_microbiome_november_2016

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November 2016 www.era7bioinformatics.com [email protected] @Era7bioinfo The Microbiome in Era7 Bioinformatics.

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November 2016

www.era7bioinformatics.com

[email protected]

@Era7bioinfo

The Microbiome

in Era7 Bioinformatics.

www.era7bioinformatics.com

Era7 Bioinformatics is The Bacterial Genomics Company

and a leader in Microbiome Analysis

www.era7bioinformatics.com

The Microbiome Revolution era

started officially on May 13th 2016

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This date The White House announced the launching of The National Microbiome Initiative

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And Era7 was there!

Our CEO Eduardo Pareja was invited to the Launching of the National Microbiome Initiative

www.era7bioinformatics.com

www.era7bioinformatics.com

Microbiome became one of the White House Important Initiatives:

• Precision Medicine Initiative

• Cancer Moonshot

• National Microbiome Initiative

www.era7bioinformatics.com

National Microbiome Initiative definition:

“Microbiomes are the communities of microorganisms that live on or in people, plants, soil, oceans, and the atmosphere. Microbiomes maintain healthy function of these diverse ecosystems, influencing human health, climate change, food security, and other factors”

www.era7bioinformatics.com

And not only The White House thinks that The Microbiome is a revolution

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www.era7bioinformatics.com

The Microbiome contains many kinds of microorganisms but the more frequently analysed are Bacteria and Archaea

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Bacteria are all over the World ……

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In the Sea

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In the soil

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In the Air

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And in all living organisms

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The Microbiome has got a great interest recently:

• Humans: in different parts of the body

• Environmental: soils, water, oceans ….

• Industrial: farms, food …..

• Places: Hospitals, tools, phones, trains…

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Microbiome in PubMed

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The Human Microbiome has been called:

“ The Second Genome “

“ The Last Organ “

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Human Microbiome facts:

• 100 times more genes than the Human Genome

• 1.5 Kilograms

• 10 times more bacteria cells than human cells in our body

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More than 10% of the small molecules in the blood come from the gut microbiome

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Human Microbiomes, many places to analyse:

• Mouth • Gut • Skin • Urinary Tract • Airways • Vagina • Human Milk • ………………………..

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A healthy Microbiome is needed

and a “bad” Microbiome is related with diseases

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• Obesity • Type 1 Diabetes • Type 2 Diabetes • Colon cancer • Asthma • Atherosclerosis • Autism • Autoimmunity • Cardiovascular Disease • Crohn • Cystic Fibrosis

Not exhaustive list of health conditions related with Gut Microbiome:

• Skin disorders • Inflammation • Fe deficiency • Multiple Sclerosis • Obesidad • Rheumatoid Arthritis • Parkinson • Sarcoidosis • Stroke • AIDS

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The Microbiome shapes The Immune System Some examples:

• Mice do not have Blood-Brain barrier when their gut is sterile.

• In Cancer Immunotherapy in mice, results depend on the Microbiome composition

• In mice, Stroke recovery depends on The Microbiome composition as demonstrated after antibiotics treatment

www.era7bioinformatics.com

The Human Microbiome is closely related with The Immune System and, thus, in Era7 Bioinformatics we can also do:

• HLA typing • TCR repertoire • BCR repertoire

www.era7bioinformatics.com

We have several approaches to analyse The Microbiome

• 16S and 18S

• Shotgun metagenomics

• Other targeted sequencing

www.era7bioinformatics.com

16S and 18S taxonomic profiling

With 16S sequencing you get info from bacteria and archaea. Is much more cheaper than Shotgun approach and very good results can be obtained.

www.era7bioinformatics.com

16S and 18S taxonomic profiling We offer two approaches:

• illumina approach

• PacBio approach

www.era7bioinformatics.com

16S and 18S taxonomic profiling

illumina approach:

You get information from 16S rRNA gene v3 and v4 variable regions sequencing an amplicon

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16S and 18S taxonomic profiling PacBio approach:

You get information from full length 16S sRNA gene sequencing an amplicon containing all the 9 variable regions:

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16S and 18S taxonomic profiling

In any approach, illumina or PacBio, our MG7 pipeline and DB7 reference database get the best results that each technology can provide

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Shotgun approach: All the DNA present in the metagenomics sample is sequenced and analysed:

You get information from all kinds of organisms but sequencing and analysis cost is higher

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Shotgun approach:

Era7 Bioinformatics uses different pipelines adapted to the objective of the analysis.

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There are also many things influencing the Microbiome: • Antibiotics • Diet • Genome • Immune System • Exercise • Pets • Infections • Age • Jet-Lag • ………..

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Era7 has a very specialised and multidisciplinary team

• Mathematicians • Software engineers • Biochemists • Microbiologists • Medical Doctors

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Data Information Knowledge

Era7isbasedinCloudComputing

www.era7bioinformatics.com

Microbiome Biomarkers will be applied very soon to Clinics

Era7 Bioinformatics is developing EHR integration and new rich interactive visualisations for clinicians in the context of our R&D project “Cardiobiome”

www.era7bioinformatics.com

El Microbioma de la Boca

Podría estar involucrado en algunos Infartos Agudos de Miocardio

Proyecto CARDIOBIOME

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Cardiobiome project:

• Cloud Microbiome analysis integrated with Electronic Health Record (EHR)

• New rich interactive visualisation tools designed for clinicians

• Microbiome analysis of Acute Myocardial Infarction as a proof of concept

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In Era7, we are expert in Microbiome based - Precision and Personalised Medicine Integrated with Immunogenomics

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• Era7 is present in The United States in Cambridge Massachusetts

• Era7 has its own specially designed methods for Microbiome analysis: MG7 and DB7

• Era7 team is very experienced in Genomics Big Data analysis

• Era7 team is based in knowledge and in research

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Era7 Bioinformatics has done Microbiome analysis projects for:

• Biotech Companies • Pharma Companies • Agri-food companies • Research Centres • Universities • Hospitals

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Era7 has launched recently a portal with Microbiome related information , from references to news and simple tools:

www.themicrobiome.com

www.era7bioinformatics.com

¿ Qué queremos hacer ? El Portal “The Microbiome”

como elemento de Marketing

SERVICE MG7

www.era7bioinformatics.com

MG7 Bioinformatics analysis for 16S

MG7 is a complete analysis tool developed by Era7 Bioinformatics oriented to provide taxonomic assignment results for big sets of sequences. MG7 pipelines of analysis are continuously being updated with the newest approaches.

www.era7bioinformatics.com

Our rRNA reference database DB7 We have built our reference database DB7 of 16S and 18S sequences based on the complete RNAcentral release 5 . RNAcentral is a general database for all the types of non coding RNA maintained by RNAcentral Consortium

MG7 Bioinformatics analysis for 16S

www.era7bioinformatics.com

Our taxonomic assignment algorithm is exhaustive We compare each read against all the sequences of our DB7 database. The taxonomic assignment for each read is based on the results of BLASTN of each read against our DB7 database.

MG7 Bioinformatics analysis for 16S

www.era7bioinformatics.com

Our algorithm for taxonomic assignment provides results for two different assignment approaches:

• Best Blast Hit (BBH)

• Lowest Common Ancestor (LCA)

MG7 Bioinformatics analysis for 16S

www.era7bioinformatics.com

MG7 provides a rich set of deliverables with 4 different types of abundance values for each of the 2 approaches (BBH and LCA) to evaluate the frequencies of bacterial and archaeal organisms:

• direct values and cumulative abundance values • absolute counts and abundance percentages

DELIVERABLES of MG7 Bioinformatics analysis for 16S

www.era7bioinformatics.com

Best BLAST Hit (BBH): • Direct Assignment, Absolute Values • Direct Assignment, Percentage Values • Cumulative Assignment, Absolute Values • Cumulative Assignment, Percentage Values

Lowest Common Ancestor Algorithm (LCA): • Direct Assignment, Absolute Values • Direct Assignment, Percentage Values • Cumulative Assignment, Absolute Values • Cumulative Assignment, Percentage Values

www.era7bioinformatics.com

DELIVERABLES of MG7 Bioinformatics analysis for 16S

MG7 provides a rich set of deliverables including tables per sample, per groups of samples, global, per ranks:

• Abundance tables per sample • All the ranks in a complete table • Abundances for each rank • Abundance tables per each defined group of samples • Abundance tables for all the samples together

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DELIVERABLES of MG7 Bioinformatics analysis for 16S

MG7 provides a rich set of deliverables including Analysis of diversity indexes

The Shannon-Wiener and Simpson’s diversity indexes are calculated for each sample.

www.era7bioinformatics.com

DELIVERABLES of MG7 Bioinformatics analysis for 16S

Comparison of groups of samples We provide statistical analysis for the study of differences between groups of samples. We use for it open tools based on R software from CRAN (The Comprehensive R Archive Network). In each case we apply the most appropriate approaches.

www.era7bioinformatics.com

DELIVERABLES of MG7 Bioinformatics analysis for 16S

Some types of statistical analysis provided for the comparison of groups of samples: • Univariate statistics (fold change analysis, t-tests, volcano plots, one-way

ANOVA, correlation analysis) • Multivariate statistics (principal component analysis , partial least

squares discriminant analysis) • Clustering (dendrograms, heatmaps, K-means clustering, self organizing

feature maps) • Supervised classification (random forests, support vector machine)

www.era7bioinformatics.com

DELIVERABLES of MG7 Bioinformatics analysis for 16S

Charts and Reports that MG7 provides

Different types of charts with the possibility of providing interactive visualizations (See our research project BIOGRAPHIKA about interactive visualizations) Complete results in compliant formats Technical reports ready to scientific publication

www.era7bioinformatics.com

DELIVERABLES of MG7 Bioinformatics analysis for 16S

MG7 workflow for 16S

• Our Reference database DB7 • Exhaustive taxonomic assignment

for each read • Two different taxonomic

assignment approaches, Best Blast Hit (BBH) and Lowest Common Ancestor (LCA)

• A complete set of deliverables

www.era7bioinformatics.com

SERVICE MG7

for full-length 16S taxonomic profiling with PacBio

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Full-length 16S taxonomic profiling with PacBio and Era7 Bioinformatics MG7

• 100% of the hypervariable regions • Obtaining 16S full gene sequences • More specific taxonomic assignments

www.era7bioinformatics.com

www.era7bioinformatics.com

Our service of Taxonomic Profiling with PacBio: Primer position in 16S gene. Includes v1 to v9 regions

Taken from www.themicrobiome.com

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From DNA or from already sequenced raw data

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Regardless your platform of preference… We can also provide further tailored interpretation services based in our Bio4j bioinformatics platform

Bio4j is a bioinformatics graph based DB including most data available in:

- UniProt (SwissProt + Trembl) - UniRef (50,90,100) - Gene Ontology (GO) - RefSeq - NCBI taxonomy - Enzyme DB

Big Data: - 2.000.000.000 relationships - 400.000.000 nodes - 1.000.000.000 properties

www.era7bioinformatics.com

www.era7bioinformatics.com

Bio4j was selected by

Google for the Google

Summer of Code 2014

www.era7bioinformatics.com

Era7 Bioinformatics can also do data integration with other -omics results and design specialised databases for your results and tailored visualisation tools

www.era7bioinformatics.com

In summary, with Era7 Bioinformatics you will have a very specialised team using a wonderful pipeline and the possibility of obtaining tailored approaches, databases and and data integration.

www.era7bioinformatics.com

Thanks for your attention !

[email protected]

@Era7bioinfo