- Coordinate standardization of procedures and protocols within the existing Human Microbiome research programs and those yet to come,
- Gather and compare the protocols used to collect, identify and process human samples and aid to develop the standard operating procedures for sample collection, identification and processing,
- Compare sequences of genes and genomes of human-associated microorganisms generated by various methodologies and approaches, and to develop standards to define sequence quality and recommend procedures to reach the standards,
- Assess the approaches and procedures used to analyze the sequence data and the associated metadata and recommend standards for data analysis.
Beside these objectives, IHMS project will aim at ensuring the optimal public access and use of the data generated by various microbiome projects.
Achievements and their impact
The final achievement of IHMS is to allow the optimization of methods for the assessment of the effects of the gut microbiome on human health through standardization of procedures and protocols within the existing and future Human Microbiome research programs.
Characterization of microbial communities associated to humans and the roles they have on human health will affect numerous fields from fundamental science, particularly human biology, to medicine or food and pharmaceutical industry. IHMS should therefore allow more efficient use of resources and faster overall progress, by improving synergy and minimizing unnecessary overlap between the numerous human microbiome research programs.
Work Packages WP
To implement the approach adopted, the project is divided into 4 strongly interacting workpackages:
- WP International Coordination & Project Management
- WP Sample Collection and processing standards
- WP Sequencing standards
- WP Data analysis
WP1: Coordination & Management
The overall objective of this work package is to set up the framework necessary for the project, in terms of data gathering and information access and exchange. This framework includes the development of IHMS website, open to the public and oriented towards the international scientific and medical communities. This workpackage also aims at focusing research efforts worldwide by presenting ongoing research projects and setting up exchange means through regular meetings and working groups (i.e. Stakeholders' platform), to devise complementarity between independent projects. To support the above activities, tools providing efficient project organization shall be developed and made available online for consortium members. INRA provides a management team to help with the overall logistics of the project.
The workpackage leader is Dr. S.D. Ehrlich from INRA.
WP2: Sample Collection Standards
The overall objective of this work package is to coordinate development of standard operating procedures (SOPs) for human microbiome sample identification, collection, and processing. For all three phases in this process, the workpackage/tasks will involve:
- Gathering protocols from past and ongoing human microbiome programs,
- Experimentally evaluating selected protocols when relevant,
- Defining optimal Standard Operating Procedures and providing accompanying recommendations.
In the first subpackage, an inventory of existing procedures applied to sample collection has been carried out through literature survey and exchanges with members of International Human Microbiome Consortium (IHMC). Focus was put on the intestinal microbiota. A subset of conditions considered relevant for comparative evaluation were selected and applied to a series of reference samples that were prepared in large numbers to further serve as reference throughout the complete procedure.
In the sample identification subset of this workpackage, it was important to develop an international consensus on the essential human metadata that needs to be linked with the samples. This includes food-frequency and food-recall questionnaires, Quality-of-Life questionnaires and further relevant information on life styles that may influence microbial colonization (taking into account the limiting factors like geographical validity). After an exhaustive inventory of the extent of Metadata that can be collected from healthy volunteers and selected groups of patients (essentially current major societal diseases), these were confronted to regulatory and ethical constraints and reduced to minimal working sets of Metadata.
In the final subset of the workpackage, an inventory of procedures for the preparation of the nucleic acids from appropriately collected samples was undertaken. Consideration was given to the requirement for high throughput treatment of large sample sets. Thus obtained DNA will eventually be analysed within WP3 and sequence data further analysed within WP4. Finally, a subset of satisfactory procedures was further selected for the assessment of inter-laboratory reproducibility. However, it must be kept in mind that the specific area of nucleic acids preparation does see constant evolutions and improvements, such that it is hardly conceivable to definitely "freeze" a procedure that will be considered as optimal in the long term.
The workpackage leader is Dr. Joel Dore from INRA.
WP3: Sequencing Standards
The overall objective of this work package is to coordinate development of standards for DNA sequence used to characterize human-associated microbial populations and to recommend procedures to generate DNA sequence of standard quality.
Sequencing of genomes of isolated microorganisms has been carried out for over a decade and can be considered a mature technology with established standards. In contrast to the latter, metagenomic sequence standards remain to be defined. Parameters such as sequencing technologies, extent of sequencing, length of the sequencing reads and single- or paired-end sequencing should be explored and optimized protocols validated with the already characterized human intestinal samples. The results shall be then transferred to WP4 for further quality control via annotation.
The workpackage leader is Dr. Eric Pelletier from the CEA Genoscope, France.
WP4: Data Analysis
The overall objective is to coordinate metagenomics data analysis protocols as well as to optimize and standardize as many as possible methods therein in order to simplify the interpretation of incoming data and to enable comparison of data produced in the many projects worldwide. Even simple agreements on how to measure the quality of such complex datasets will boast the analysis options for the vast amount of data being produced.
In this workpackage, different analysis pipelines using several sequenced samples shall be compared and the efficiency and quality of various methods and steps analyzed to propose minimum analysis standards. The range of these standards should include categories like metadata relevance, annotation and sequence quality, functional and phylogenetic composition and visualization options.
The workpackage leader is Dr. Peer Bork.