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It is easy to be preoccupied with the day-to-day tasks of a proj= ect, particularly when development work is progressing full pace. However, = it is interesting to look more widely and consider the impact our work has = had on the scientific community.
HELM was released in 2013, with a single user =E2=80=93 Pfizer (who invente=
d it), but were shortly followed by ChemAxon and a steady stream of organis=
ations which represent a wide section of the informatics community. We have=
also gained recognition from regulators who endorsed HELM as an acceptable=
format in ISO 11238.
The list of HELM users is now very healthy, and we appreciate our enthusias=
tic and engaged community. Here are some of the groups who are using HELM.<=
/p>
GSK is using of the Pistoia Alliance=E2=80=99s Hierarchical Editing Lang= uage for Macromolecules (HELM) notation to represent therapeutic large mole= cules in its bio-registration system, facilitated by the deployment of Dass= ault Syst=C3=A8mes BIOVIA=E2=80=99s Biological Registration solution. GSK s= cientists at sites around the world will use the system.
=E2=80=9CThere is a gap in the space that HELM now covers where there we= ren=E2=80=99t really any alternatives. It was desirable for GSK to be on a = standard rather than create our own notation, and to partner with the Pisto= ia Alliance and other companies to develop that standard.=E2=80=9D Leah O= =E2=80=99Brien, Business Consultant, GSK.
Pistoia-Alliance-HELM-GSK-BIOVIA-= Case-Study.pdf
Internal registration systems and tools are all based on HELM.
Merck has been slowly adopting the HELM notation across our Discovery Ch= emistry Modalities organization focusing first on simple linear peptides an= d oligonucleotides. Using the Pistoia HELM editor for creation, editing and= registration of monomers and chemical modifiers, our Modalities chemists c= an now work confidently with their monomers across multiple environments in= cluding our biopolymer registration system, our BioviaDraw platform and our= tools within Insight for Excel. In 2018 we anticipate incorporating comple= x, macrocyclic biopolymers into the HELM supported workflows, peptide metab= olite identification support and antibody-peptide conjugates. All of this f= acilitated by the easy to use tools leveraging HELM notation as a foundatio= n.
Novartis makes extensive use of HELM for nucleotide registration and ana=
lysis. The open-source HELM tools are integrated with the internal informat=
ics landscape.
Yohann Potier said, =E2=80=9CHELM allows Novartis to accurately describe it=
s chemically-modified constructs using an industry standard for registratio=
n.=E2=80=9D
As the originators of the HELM standard, Pfizer has based their entire m=
acromolecular registration infrastructure on HELM and its associated biomol=
ecule toolkit.
Sergio Rotstein said, =E2=80=9CWhile the enablement of biomolecular registr=
ation was already of great value to Pfizer, the establishment of HELM as an=
industry standard provided even greater value by facilitating cross-compan=
y interoperability and biomolecular data exchange, a very desirable outcome=
in our increasingly collaborative industry=E2=80=9D
Starting with HELM Roche has developed the HELM Antibody Editor (HAbE) t=
o enable especially the convenient handling of complex antibody in innovati=
ve formats for their analysis, visualization, manipulation and registration=
.
Most recent is the implementation of HELM2 at Roche to describe, register a=
nd manage therapeutic oligonucleotides and their derivates. This was facili=
tated by the improved monomer handling and support for ambiguous nucleotide=
s within the HELM 2 toolkit.
Wave is in the process of adopting HELM notation for its monomer da= tabase and converting all of its registered molecules to the HELM stan= dard. Wave is primarily focused on the oligonucleotide chemistry space, and= an interest in defining the use of stereochemistry in phosphorothioate bac= kbone chemistries. The HELM notation is a chemically precise and flexible o= pen source "building block" system that allows us to quickly assemble and r= ender complex molecules and their properties.
ACD/Labs supports HELM across our portfolio, from the ACD/Labs Bio= sequence tool (ACD/ChemSketch) to our array of software for analytical chem= istry ACD/Spectrus, and the Luminata CMC project decision support applicati= on, to the recently announced Katalyst D2D for high throughput and parallel= experimentation. Notations for biomolecules ranging from small peptides to= whole antibodies can be imported from HELM and xHELM files and exported in= HELM file format. =E2=80=9CHELM notation is the cornerstone of our expande= d molecular characterization efforts, from small molecule to biologics=E2= =80=9D,- says CEO Daria Thorp.
Benchling supports chemically m= odified oligonucleotide design, analysis, and characterization in a high-th= roughput manner using HELM notation. By standardizing on HELM in a single p= latform, R&D teams can centralize experimental results, standardize oli= go sequences and naming uniqueness during registration, and collaborate wit= h teammates more effectively. HELM allows scientists using Benchling to est= ablish a scalable common language across organizations, improve data qualit= y, surface real-time scientific insights, and accelerate the speed of the f= ull therapeutic lifecycle. Benchling users can also interconvert ITD syntax= to HELM sequences making it easier to share designed sequences with vendor= s and collaborators.
Applications use Biovia=E2=80=99s proprietary SCSR (Self-Contained Seque= nce representation, an extension of the V3000 molfile) format, but there is= extensive ability to import, export and convert to and from HELM. Pipeline= Pilot Chemistry Collection contains importers and exporters, HELM readers = and writers including XHELM, and components to interconvert between macromo= lecules represented by HELM, full chemistry and SCSR. HELM support is avail= able in Insight, the Draw and Pipette sketchers, biological registration an= d the chemistry cartridge.
Certara=E2=80=99s D360 application for scientific informatics supports d= iscovery research scientists through self-service access data access, integ= rated analysis and data visualization capabilities combined with coll= aboration tools to improve data driven decision making. D360 has been deplo= yed in support of small molecule and research into other modalities s= uch as antibodies, ADCs, oligonucleotides, and peptides. D360 supports the = use of HELM notation for searching, filtering and rendering other modalitie= s. More advanced functionality, such as sequence formatting, alignmen= t and clustering based on HELM representation allows users to determi= ne and exploit sequence-activity relationships.
Biomolecule Toolkit and the macromolecule sketcher BioEddie are natively=
supporting the HELM standard. The tools provide capabilities for managing =
a centralized monomer library, registering and performing uniqueness checks=
of macromolecules, generating a HELM notation from small molecule represen=
tations and sequences, and representing modalities with partially or fully =
unknown chemical structures.
Roland Knispel, Project Lead for Biologics Informatics at ChemAxon, said, =
=E2=80=9COur HELM-based tools are helping our customers to manage chemicall=
y modified sequence-based modalities. A single environment for various type=
s of modalities, improved data quality and utilizing an industry-wide stand=
ard for data exchange are the key benefits reported back to us by our users=
. By market demand our platform is now being integrated into solutions prov=
ided by IDBS and other partners.=E2=80=9D
Dotmatics has adopted the Pistoia Alliance=E2=80=99s HELM notat= ion as part of its biologics discovery suite. Dotmatics=E2=80=99 b= iological registration system, Bioregister, in= tegrates the HELM Web Editor to create and edit sequences in HELM notation.= Bioregister also generates, stores, and reads= /writes HELM notation. This allows users to work with their HELM-defined en= tities within the Dotmatics Suite and also to exchange HELM-format data wit= h other HELM-compliant systems. Additionally, Dotmatics=E2=80=99 a= nalysis and visualization application, V= ortex, reads HELM notation and from this generates oligomeric represent= ations, allowing advanced analytical techniques to be applied directly to H= ELM-represented entities.
IDBS leverages ChemAxon=E2=80=99s Biomolecule Toolkit and BioEddie in it=
s E-WorkBook suite and therefore includes HELM support.
Paul Gouldson, Vice President Strategic Solutions said, =E2=80=9CIDBS has b=
een supporting open standards in EWB since its inception. We use and develo=
p integrations to open source tools and have supported examples with AniML,=
HELM, ADF, SVG and HTML tools.=E2=80=9D
The HELM format is supported by Sugar&Splice both for reading and wr= iting peptides and nucleic acids, thus enabling conversion of all-atom stru= ctures from SMILES (for example) through HELM and back to SMILES. This supp= ort includes inline HELM (allowing structural data to be roundtripped even = when monomers are missing from the HELM database), xHELM and partial suppor= t for HELM 2.0 ambiguity codes. The NCBI uses Sugar&Splice to generate = HELM strings for all biopolymer entries in PubChem.
RDKit includes the ability to convert DNA, RNA and peptides to and from = HELM and a large number of other notations including: FASTA, PDBBlock and s= tandard sequence notation.
PerkinElmer integrated the Pistoia Alliance HELM standard into ChemDraw= =C2=AE, enabling chemists and biologists to easily describe complex molecul= ar structures, rapidly create biopolymeric structures, and share their info= rmation in an industry-standard, publication-ready format. =E2=80=9CWe look= forward to continuing to work with HELM as a standard to better serve the = research community by providing modern tools that foster collaboration and = enable faster discoveries,=E2=80=9D says Pierre Morieux, ChemDraw Global Ma= rketing Manager at PerkinElmer.
Scilligence supports HELM monomer management and sketching in their wide= range of informatics solutions including Scil= ligence ELN and RegMol/BioAssay. Scil= ligence is the developer of the HELM Web Editor which works to further stand= ardize HELM notation and facilitate the exchange of information between res= earchers.
Being involved in the HELM tool development from the early hours, quattr= o research provides solutions for registration of biomolecules based on HEL= M notation. With a focus on antibodies and ADCs (antibody-drug-conjugate), = we have developed the HELM Antibody Editor (HAbE) together with Roche. The = xHELM format for data exchange, the ambiguity support of the HELM2 toolkit = and a monomer service are additional Pistoia hosted projects developed and = maintained by quattro research, in addition to our internal development and= research. Many of these tools are now open source and hosted on GitHub, ma= de available to all who are looking into adopting HELM as a standard
ChEMBL is one of the largest public drug discovery databases, containing=
information about approved drugs, clinical candidates and lead optimizatio=
n data, including 1.7 million distinct compounds and more than 11,000 targe=
ts.
=E2=80=9CA large proportion of new drugs are now biotherapeutics, but many =
could not be adequately represented by our traditional sequence or structur=
e formats. HELM gives us a great solution, allowing us to accurately descri=
be drugs such as modified peptides and antibodies=E2=80=9D says Anna Gaulto=
n, Senior Data Integration Officer for the EMBL-EBI Chemogenomics Team.
The ChEMBL database team have worked with the HELM project on methods to fr=
agment peptide structures and define new monomers. These have been used to =
converted more than 20,000 natural and modified peptide structures to HELM =
and create a publicly-available library of more than 2800 peptide monomers.=
PubChem is an open chemistry database at the National Institutes of Heal=
th (NIH), which provides information on chemical structures, identifiers, c=
hemical and physical properties, biological activities, patents, health, sa=
fety, toxicity data, and many others to several million scientists worldwid=
e.
Pubchem contains over 500,000 structures represented in the HELM notation. =
Many of these are complex, for example, only 65% of the HELM peptides are e=
xclusively made up of amino acids.