The Pistoia Alliance and quattro research GmbH announce ambiguity support for HELM

Munich, April 4, 2016 – The Pistoia Alliance, a global alliance of life science companies, vendors, publishers, and academic groups and quattro research GmbH are pleased to announce the release of a major new extension to the HELM notation standard and toolkit. The new functionality enables HELM to support the representation of biomolecules with some structural uncertainty or ambiguity.

As the therapeutic utilization of complex and non-standard biomolecules has become commonplace in drug discovery R&D, scientists have struggled to represent these entities in their information systems, forcing them to use very non-standard “pick and mix” approaches that include multiple nomenclatures and textual descriptions. HELM, the open biomolecular representation standard, has solved this problem by providing a means to represent multiple types of complex macromolecules (e.g. nucleotides, proteins, antibodies and antibody-drug conjugates) including those that contain non-natural elements such as chemically modified amino acids.

The Pistoia Alliance formalized the HELM notation, originally created by Pfizer scientists, as an open standard in early 2013 and publicly released the related software toolkit and editor to the Open Source community. Since its release, HELM has benefited from a growing ecosystem of global adopters and contributors that includes organizations such as ACD Labs, Arxspan, Biomax, Biovia, BMS, ChemAxon, EMBL-EBI, eMolecules, GSK, Ionis, Merck, NextMove, Novartis, Pfizer, quattro research, Roche, and Scilligence.

While the original HELM solved the problem of representing unnatural complex biomolecules, it held the basic assumption that a scientist would know everything about the structures being represented. In biology, however, this is not always the case, as a various types of ambiguity or uncertainty may exist in some of these structures. A typical example is when the exact conjugation site of an antibody-drug conjugate cannot be determined. This left scientists with a difficult choice: either record a best guess of what the structure is, or simply describe the structure textually instead of structurally, creating a gap in their corporate structural registries. HELM 2.0 enables scientists to incorporate into their structural representation a systematic description of a number of forms of ambiguity, thus allowing for the rigorous representation of structures, even when uncertainty is present.

In addition to the representation of ambiguity, the HELM 2.0 toolkit provides a couple of additional enhancements that will make it easier for companies to integrate HELM into their infrastructure:

  1. An API that allows the toolkit to leverage different cheminformatics software libraries
  2. A set of web services that abstract the toolkit functionality from the toolkit code to facilitate calls to and from other software

“HELM had already significantly improved researchers’ ability to rigorously represent complex macromolecules. However, there was still a gap when it came to dealing with the very real-world scenario of structural uncertainty or ambiguity. Through this partnership with quattro research, we have implemented a pragmatic solution to this problem that further enhances the capabilities and applicability of the standard,” said Sergio Rotstein, Director of Research Business Technology at Pfizer and Domain Lead for the Pistoia Alliance HELM initiative.

Markus Weisser, Managing Director at quattro research GmbH adds: “HELM is designed as an open source project. Hence, in addition to ambiguity support, it was important that we remove third party dependencies and provide a more service-oriented architecture. This lowers the barriers to utilizing HELM and contributing to its development, and will enable more individuals and organizations to join the HELM community. Over the past two years, quattro research has become a leading expert in HELM and its extensions. Previously we helped to develop the Exchangeable HELM (xHELM) extension and contributed to the development of the HELM Antibody Editor. We are very proud to have built on this work in the development of HELM 2.0.”

About quattro research GmbH:

quattro research GmbH is a software and service company located in Munich, Germany. quattro research offers services and products for data management in the pharmaceutical, chemical, and biotech industry. The primary focus of the company is the development of tools and services for compound registration and analysis of biological data. Within several projects, quattro research developed extensive knowledge in the management and registration of biologics, e.g. antibodies and peptides. For further information see www.quattro-research.com or email weisser@quattro-research.com.

Pistoia Alliance partners with quattro research GmbH to implement “Ambiguous HELM”

Munich, October 14th, 2015 – The Pistoia Alliance, a global alliance of life science companies, vendors, publishers, and academic groups, has selected quattro research GmbH to implement the HELM 2.0 project (“Ambiguous HELM”). This initiative will enable HELM to represent biomolecules in which some aspects of the structural composition or assembly are not fully determined.

Scientists have struggled to represent non-standard biomolecules in their systems leading to “pick and mix” approach of multiple nomenclatures and textual descriptions. HELM, the open standard, enables the representation of multiple types of complex macromolecules including nucleotides, proteins, antibodies and drug-antibody conjugates including ones containing non-natural elements.

Created by a team at Pfizer, the Pistoia Alliance formalized the HELM notation as an open standard in early 2013 and publicly released software tools to the Open Source community. Since its release, HELM has benefited from a growing range of global adopters and contributors, which includes ACD Labs, Arxspan, Biomax, Biovia, BMS, ChemAxon, EMBL-EBI, eMolecules, GSK, Lundbeck, Merck, NextMove, Novartis, Pfizer, quattro research, Roche, and Scilligence.

While the existing HELM approach solves the problem of representing unnatural complex biomolecules, it still assumes that the scientist knows everything about the structure. In biology this is rarely the case, with the outcome of experiments subject to a number of uncertainties. Currently scientists have a difficult choice: either imply they have all the information and guess at a structure, or record a textual description and put no structural information in their corporate databases. Ambiguous HELM allows the structural information that is available to be captured in a useful way, while also identifying what is not known.

The HELM 2.0 project aims to implement a number of enhancements to the current HELM definition and open source codebase:

  1. Extend the HELM notation and the HELM toolkit to allow for the representation of ambiguous macromolecules.
  2. Create an API which allows the toolkit to access different chemical libraries.
  3. Create web-services for the toolkit to abstract the toolkit functionality from the code implementation.

“HELM has already delivered a practical way for researchers to represent complex biomolecules computationally. Through our partnership with quattro research, HELM will now be able to gracefully deal with the all-too-common situation of entities with uncertain or ambiguous structural features, an important expansion in the usability – and consequently – the adoptability of the technology” said Sergio Rotstein, Director of Research Business Technology at Pfizer and Domain Lead for the Pistoia Alliance HELM initiative, comment.

Markus Weisser, Managing Director at quattro research GmbH added: “HELM is designed as an open source project. Hence, it is important that we now start to remove third party dependencies and provide a more service-oriented architecture. This will lower the barriers to contributing to the development of HELM and attract even more companies to join the HELM community. During the last one and a half years, quattro research has become a leading expert in HELM and its extensions. We have helped to develop the extension xHELM and contributed to the development of the HELM Antibody Editor. We are very proud that the Pistoia Alliance has chosen us to implement HELM 2.0 and look forward to another successful collaboration.”

About the Pistoia Alliance:

The Pistoia Alliance is a global, not-for-profit alliance of life science companies, vendors, publishers, and academic groups that work together to lower barriers to innovation in R&D. Our projects transform R&D innovation through pre-competitive collaboration. We bring together the key constituents to identify the root causes that lead to R&D inefficiencies. We develop best practices and technology pilots to overcome common obstacles. Our members collaborate as equals on open projects that generate significant value for the worldwide life sciences community. www.pistoiaalliance.org.

About quattro research GmbH:

quattro research GmbH is a software and service company located in Munich, Germany. quattro research offers services and products for data management in the pharmaceutical, chemical, and biotech industry. The primary focus of the company is the development of tools and services for compound registration and analysis of biological data. Within several projects, quattro research developed extensive knowledge in the management and registration of biologics, e.g. antibodies and peptides. For further information see de.quattro-research.com or email weisser@quattro-research.com.

The Pistoia Alliance Releases Exchangeable HELM

Wilmington, DE, July 1, 2014 -The Pistoia Alliance and quattro research are pleased to announce the release of an extension to the HELM biomolecular representation standard.

HELM (Hierarchical Editing Language for Macromolecules) enables the representation of a wide range of biomolecules (e.g. proteins, nucleotides, antibody drug conjugates) whose size and complexity render existing small-molecule and sequence-based informatics methodologies impractical or unusable. HELM solves this problem through a hierarchical notation that represents complex macromolecules as polymeric structures with support for unnatural components (e.g. unnatural amino acids) and chemical modifications. The set of monomers that comprise a HELM polymer are defined in a monomer database that is generally centralized within an organization. However, different organizations are likely to employ different monomer naming conventions, thus creating a challenge when exchanging structuresbetween them in HELM format. To address this, the Pistoia Alliance and quattro research have worked together to develop an „Exchangeable HELM“ file format which allows a HELM biomolecule set to include the structure definition of its component monomers, in essence combining the biomoleculesand relevant subset of the monomer database into a single, portable file. The package released today includes updates to:

  • The HELM specification document.
  • The software toolkit that includes all the functionality needed to implement a HELM-based system.
  • The fully functioning macromolecule editor that enables the drawing of macromolecules and generation of HELM notation.

According to Sergio Rotstein, a Director in Pfizer’s Research Business Technology organization and Domain Lead for the Pistoia Alliance HELM initiative, „This is the logical next step in the evolution of the HELM standard. Today we have enhanced the versatility of HELM, adding support for a key requirement from organizations in an increasingly collaborative environment. Institutes, CROs, software vendors and IT service providers can now more easily exchange biomolecule data and information, which ultimately benefits our whole industry.“

Markus Weisser, Managing Director of quattro research, stated „The development of the exchangeable HELM format within the Pistoia Alliance was a win-win partnership for all participants. We received excellent support from the Pistoia Alliance and very positive feedback from our customers on this new standard. This further evolution of HELM is a major step for utilizing all the potential of biomolecules in the therapeutic area.“ John Wise, the Pistoia Alliance’s Executive Director, said, „This is an exciting day for the Pistoia Alliance. Macromolecules are increasingly important as therapeutic agents to treat or palliate human disease and this enhancement increases the impact that HELM has on its growing user base. By developing HELM beyond the original Pfizer implementation the Pistoia Alliance makes another contribution to lowering the barriers to innovation in life science R&D.“ For further information about HELM please contact: Sergio Rotstein at sergio.rotstein@pistoiaalliance.org or visit our web site, www.OpenHELM.org. About the Pistoia Alliance The Pistoia Alliance is a not-for-profit, cross-company, members‘ organization, formally incorporated in the State of Delaware. It is committed to lowering the barriers to innovation in life sciences R&D by improving the interoperability of R&D business processes through precompetitive collaboration. It draws its membership widely from life science R&D including Pharma R&D, commercial information providers, technology companies and publicly-funded research institutes. The Pistoia Alliance creates a virtual, open-innovation community by bringing together the key stakeholders to identify the root causes that lead to life science R&D inefficiencies and then develops best practices, technology implementations and standards to overcome these common obstacles.For further information about Pistoia please contact: Claire Bellamy at +44 7508 209365 (UK) and claire.bellamy@pistoiaalliance.org or visit our Web site, www.pistoiaalliance.org About quattro research GmbH: quattro research GmbH is a software and service company located in Munich, Germany. quattro research offers services and products for data management to the pharmaceutical, chemical, and biotech industry. The primary focus of the company is the development of tools and services for compound registration and analysis of biological data. In several projects, quattro research has developed extensive knowledge in the management and registration of biologics, e.g. antibodies and peptides. For further information see de.quattro-research.com or email weisser@quattro-research.com.

Pistoia Alliance partners with quattro research GmbH to design and implement „Exchangeable HELM“

Munich, February 3rd, 2014 – Pistoia Alliance, a global alliance of life science companies, vendors, publishers, and academic groups – selected quattro research GmbH to design and implement an extension to the HELM standard and its associated tools.

The Hierarchical Editing Language for Macromolecules (HELM), an emerging notation standard, enables the representation of a wide range of biomolecules (e.g. proteins, nucleotides, antibody drug conjugates) through a hierarchical notation that represents complex macromolecules as polymeric structures with support for unnatural components (e.g. unnatural amino acids) and chemical modifications. Created by Pfizer scientists, the Pistoia Alliance formalized the HELM notation as an open standard in early 2013 and publicly released software tools to the Open Source community, which now serve as the reference implementation of the HELM standard.

At present HELM relies on externally defined monomer definitions e.g. for chemical modifiers. Within organisations such as Pfizer, monomer definitions are usually held within central databases, while in the HELM editor these definitions are contained in a publically available XML file which is copied onto the user’s machine when the software is used for the first time.

This external monomer definition means that it is not possible to move information from one organisation to another using only the HELM notation. The purpose of Exchangeable HELM is to solve this problem. The project will deliver the extension of the HELM notation, the HELM toolkit and the HELM editor with a self-contained data format. Development will start in January 2014.

„Mid 2013 we started to work with the Pistoia Alliance to be more closely involved in the standardization process of chemical and biological data exchange. Together with a customer we are currently working on extensions of the HELM editor to suit the needs of scientists in antibody and complex protein research. Within this project, we gained insight into the internal structures and classes of the HELM toolkit and the editor and are able and willing to further participate in the evolution of HELM to become a widely accepted standard“, said Dr. Markus Weisser, Managing Director at quattro research and project leader of Exchangeable HELM.

„We are excited to be working with quattro research on this important development of the HELM standard. Exchangeable HELM will increase the flexibility of HELM enhancing its value as the notation of choice for large molecules in general and those hard to represent cases in particular“, said Sergio Rotstein, a Director in Pfizer’s Research Business Technology organization and Domain Lead for the Pistoia Alliance HELM initiative.

About Pistoia Alliance:

The Pistoia Alliance is a global, not-for-profit, precompetitive alliance of life science companies, vendors, publishers, and academic groups that aims to lower barriers to innovation by improving the interoperability of R&D business processes. Pistoia Alliance differs from standards groups because it brings together the key constituents to identify the root causes that lead to R&D inefficiencies and develops best practices and technology pilots to overcome common obstacles. For further Information see www.pistoiaalliance.org or email info@openhelm.org.

About quattro research GmbH:

quattro research GmbH is a software and service company located in Munich, Germany. quattro research offers services and products for data management in the pharmaceutical, chemical, and biotech industry. The primary focus of the company is the development of tools and services for compound registration and analysis of biological data. Within several projects, quattro research developed extensive knowledge in the management and registration of biologics, e.g. antibodies and peptides. For further information see de.quattro-research.com or email weisser@quattro-research.com.