Cancer Biomarkers

21/08/2014

When tackling any disease, the first step is to learn what signals its presence and what else these signs can mean. In discussing cancer, these signs are referred to as cancer biomarkers. Some organisations define a biomarker as a molecule that the cancerous tumor has secreted into the body, a direct bi-product of the presence of the disease. But others have a broader definition, using the term biomarker to describe both these molecules and the range of chemical and biological reactions produced by the body as it finds itself under attack from within.

The ability to search out these markers is vital both to the treatment of cancer and to research into the most effective cures. So what role does a marker like this play in cancer research and medicine?

Biomarkers in cancer medicine

There are a range of different uses of biomarkers in the treatment of cancer.

ASSESSING RISK

Biomarkers can come into play before someone even becomes a patient. Certain biological signs, in particular the presence of specific sets of genes, can indicate that a person will be particularly prone to a certain sort of cancer. Testing people with a family history of cancer can give them a warning if they are likely to suffer from the disease, and so take steps to prevent it.

Rather than allow cancer to emerge and flourish unnoticed through the natural course of events, someone who knows that they are genetically at risk can make preventative changes. They can alter parts of their lifestyle likely to trigger the cancer they are predisposed to, and which while safe for others might be potentially dangerous for them. They can also seek regular testing for cancer, catching it early if it arises and so allowingmore effective treatment of the cancer.

DIAGNOSIS

Biomarkers can be tested to identify the presence of cancer and to tell doctors more about the way it is developing. This is particularly useful in determining whether a second cancer is the result of circulating tumor cells from the first, or whether it has taken root in the body independently.

PROGNOSIS AND TREATMENT PREDICTIONS

Because they can provide a lot of information about the disease, biomarkers can be used to create a prognosis for the cancer and to predict the likely impact of any given treatment. Certain biomarkers are associated with better survival rates or cancers that respond well to particular treatment. If the doctor treating a patient knows that their cancer shows particular features, and that a drug targets cancers with those features, then the chances of successful treatment dramatically increase. Equally, if they can tell that a patient will have trouble metabolising a drug then they can choose a more suitable alternative.

MONITORING THE EFFECTIVENESS OF TREATMENT

A lot of research is currently underway into the use of biomarkers as a sign of how effectively a treatment is working. As the cancer causes particular biomarkers, and the body produces others in response, a rise or fall in their presence can be a sign of progress. Other ways of monitoring treatment are often costly and take up equipment that could be used for other patients, so biomarkers could save hospital resources and thus lives.

RECURRENCE

Some biomarkers provide indicators of whether cancer is likely to recur. This can help in deciding how closely to monitor a patient after treatment has ended.

Biomarkers in cancer research

Given their importance in cancer treatment, it is hardly surprising that biomarkers play a significant role in cancer research.

In trials of cancer drugs, as in those for other medicines, it is not always possible to see the disease through to its finish, whether that is a cure or the failure of the drug and so the patient’sdeath. In the latter case in particular, trials may need to be stopped and new treatment begun.

Cancer testing is particularly challenging, as the long duration of the disease can prevent testing through its whole course, and invasive biopsies are often the only way to directly examine a patient’s cancer.

Given these issues, biomarkers are often used as stand-ins signifying whether or not a treatment is working. If the biomarkers indicate that the treatment is affecting the cancer then researchers can avoid the need for long trials or direct inspection of the tumor.

Analysing the HLA region for cancer research

At Omixon we are specialized in the analysis of Human Leukocyte Antigen (HLA) genes using Next Generation Sequencing (NGS) data. The HLA region is probably the most complex region in the entire genome, with a high number of biomarkers and disease associations. Interestingly, the relevance of HLA genes for many cancers is becoming increasingly clear.

For example there is evidence for a role of specific HLA-A genotypes as high risk factors for the development of Chronic Lymphocytic Leukaemia (CLL). The specific mechanism is not clear but it is hypothesized that certain HLA variants may indirectly lead to abnormal proliferation of B-Cells.
Furthermore, some HLA genotypes have been identified as high risk factor for cervical cancer whereas others are reportedly associated to reduced risk of developing certain cancers, such as breast and oral cancer

Omixon can help both scientists and clinicians to better analyse the relevant HLA genes and contribute to a deeper understating of this complex genomic region.

Omixon Launches Holotype HLA™ for NGS-based HLA Genotyping

18/07/2014

Omixon announces the launch of Omixon Holotype HLA™ – a combination Assay and Software product that leverages the power of Next Generation Sequencing (NGS), for use on the Illumina® MiSeq sequencing platform. The assay and software have been optimized through cohesive collaboration with the Monos lab at The Children’s Hospital of Philadelphia (CHOP) and will include a new software product, Omixon HLA Twin™, that features two different algorithms for orthogonal validation by data analysis and the most accurate high-resolution genotyping available.

“This new approach sets the stage for the thorough and accurate characterization of the HLA genes,” says Professor Dimitri Monos, Director of the Immunogenetics Laboratory in the Department of Pathology and Laboratory Medicine at CHOP. “These genes are critical for any antigen-specific immune response and found to be very important for transplantation, have been associated with many autoimmune diseases, play a critical role in infectious diseases and most recently their relevance to pharmacogenomics has been demonstrated, as they influence immunological reactions to particular medications. It is very likely that this new technology will provide additional insights that may further elucidate the role of these genes/molecules in each of these disciplines and beyond in rather surprising and unpredictable ways.” The assay provides targeted amplification and library preparation reagents for the whole gene coverage of HLA-A, B, C and DQB1, and partial coverage for HLA-DRB1.

The resulting Illumina data provides even and deep coverage, allowing Omixon’s new HLA Twin software to fully resolve phase for both alleles at each locus and provide completely characterized novel allele sequences. Professor Monos says, “We are delighted with the Omixon HLA Twin software and have been particularly impressed with the modifications to the software for handling our protocol whereby all amplified HLA loci are pooled together and processed as a single library decreasing cost and saving time without compromising accuracy of HLA genotyping.” An important feature of Omixon HLA Twin is the ability to resolve complex genotypes with high accuracy to the third or even fourth field level.

Dr. Attila Berces, Founder and Chairman at Omixon says, “Professor. Monos’ protocol is as much art as it is science. It’s wonderfully simple and a huge leap forward in terms of usability for HLA labs looking to keep pace with the latest technologies.” Similarly, he notes that “At Omixon, we have developed assay-specific features within the software that gives scientists the highest possible confidence in their genotyping results, a transparent system of notification flags to assist a clinical analyst with difficult to resolve alleles, and the benefit of two independent algorithms for analyzing the sequence data.” Omixon’s software implements two algorithms that are not just different, but orthogonal in their approach to resolving HLA genotypes, providing the only turnkey solution for analyzing HLA genotypes from NGS data.

The adoption of Omixon Holotype HLA by labs internationally provides the opportunity to improve transplantation outcomes through a more refined assessment of donor compatibility, and will expedite the donor selection process from bone marrow registries. Dr. Berces notes that “Bone marrow transplantation in particular is one of the most expensive medical procedures with high mortality rates. Omixon’s new product should help to better understand the genetic factors of successful transplantation and thus improve not only patient outcome but economic efficiency of the procedure”. In addition to its role in transplantation, Omixon Holotype HLA is an advanced tool for disease association studies in immunology and infectious diseases, including therapeutic response studies for immunotherapeutics and adverse drug response studies.

Invitation to the Early Access Program for Holotype HLA

Omixon is making Holotype HLA available for purchase through an Early Access Program (EAP) to selected HLA laboratories across the globe that are planning to migrate to NGS-based HLA genotyping. Please contact Omixon’s CEO, Tim Hague directly (tim.hague@omixon.com) to enquire about the terms of participation. EAP members will be accepted until the maximum capacity is reached.

Contact sales@omixon.com, or visit our Holotype HLA™ product page for more information

Omixon Celebrates a Successful EFI 2014

03/07/2014

Omixon took a team of 8 to the 28th EFI (European Histocompatibility and Immunogenetics) Conference, held in Stockholm. Omixon’s “A Team” of defenders (science nerds), midfielders (marketing bods) and strikers (sales weenies) were superbly captained by the indefatigable Craig Funnell (Director of Sales and Marketing), and brought super-sub Attila Berces (Founder and Chairman) and water bottle carrier Tim Hague (CEO) along for the ride.

There were over 1200 attendees altogether from all over the world, and much of the discussion centred around HLA Typing using NGS data. There was a huge amount of interest in the recent collaboration announced between Omixon and the Children’s Hospital of Philadelphia, and the team at the Omixon booth were rushed off their feet dealing with enquiries about the impending Illumina-based, combination Assay and Software HLA product and demonstrating the Omixon HLA Typing software. There was also keen interest in a poster describing elements of the Omixon HLA algorithms.

CEO Tim Hague commented afterwards: “We were humbled and gratified by such a positive response to our collaboration with CHOP. We’re very excited about the possibilities for our new HLA kit product range. We also drank too much wine at the One Lambda party.”

Visit the EFI website to read more…

Omixon Target Release Notes 1.9.1

01/07/2014

We are happy to let you know that a new version of Omixon Target is now available, including updated features and further improvements.

Feel free to download the new version using the plugin on our website. When installing, select the ‘upgrade’ option to renew an existing installation.

If you have the server version of Omixon Target, our support team will contact you shortly with an update message.

Major New Features (HLA typing module)

Credit re-usability – samples analysed with the new version can be re-analysed indefinitely with different sets of parameters, one sample ultimately costs 1 credit
- Restriction – currently reanalysis will overwrite existing results, so these should be exported beforehand
- Restriction – there is currently no comparison of results between two analyses, this feature is coming soon
Improved ambiguity handling in HLA typing – in some cases this will lead to more ambiguity in the results

Minor Improvements (HLA typing module)

Aligner performance improved
Improved custom candidate management in the Genome Browser
Assignment of imbalanced candidates
Export-import now supports every alignment method
New pager for easier task sorting in Process Manager
Updated Help
Bugfixes and other improvements

As usual, all feedback and comments are welcome.

Sincerely,

The Omixon Team

Technical Assistance: support@omixon.com
Product Information: sales@omixon.com

NGS-Based HLA Genotyping: Omixon and CHOP Collaborate

04/06/2014

Omixon is very proud to announce an exclusive licensing agreement with The Children’s Hospital of Philadelphia (CHOP) to commercialize a new Next Generation Sequencing (NGS) HLA genotyping assay, for use on the Illumina® MiSeq sequencing platform.

The Illumina-specific HLA genotyping protocol was developed by Professor Dimitri Monos, Director of the Immunogenetics Laboratory in the Department of Pathology and Laboratory Medicine at CHOP and his group. The assay provides targeted amplification and library preparation reagents for the whole gene coverage of HLA-A, B, C and DQB1, and partial coverage for HLA-DRB1. “This new approach addresses a 60-year-old problem,” says Professor Monos. “Since the discovery of HLAs in the early 1950s, it has been a challenge to accurately and thoroughly characterize HLA gene sequences. We have now used next-generation sequencing tools to significantly advance HLA typing.”

HLA genes are the most complex gene family known in the entire human genome. Gene sequences for HLAs are extremely polymorphic – highly variable – to a degree not adequately captured by conventional typing tests such as SSO/SSP or Sanger Sequence Based Typing (SBT). SBT frequently provides ambiguous and/or limited results, by sequencing only part of the HLA genes and failing to distinguish among different alleles due to difficulty with resolving the phasing of those alleles. In addition, preliminary testing is frequently followed by a second level of reflexive testing, adding expense and time to the HLA typing process. “Since sequence-based typing by Sanger was adopted for the characterization of the HLA polymorphisms, the number of known HLA alleles has been growing exponentially. This has actually enhanced frustration as initial typing results include an increasing number of ambiguities and labs need to resort to additional reflexive testing in order to fully resolve them. This is the first technology that gives results free of any current or future ambiguities”, says Professor Monos.

While the potential of NGS to provide the first fully resolved, nucleotide level characterization of HLA has been understood for several years, it has been a challenge to convert this potential into a practical solution that would be both easy to work with and fully exploit the benefits of NGS technology. To address these challenges, Professor Monos and colleagues developed a new protocol for HLA genotyping using NGS data from the Illumina MiSeq platform. “This is a new, disruptive technology, with the potential to transform research and clinical practice, in transplantation and other fields,” said Robert Doms, Pathologist-in-Chief at CHOP.

The resulting Illumina data provides even and deep coverage, allowing Omixon Target™ HLA Typing software to fully resolve phase for both alleles at each locus and provide completely characterized novel allele sequences. Dr. Attila Berces, Founder and Chairman at Omixon describes the technology “This assay solves many challenges including preferential allele amplification, uneven amplification of key exons and fragment size problems that most people who develop HLA assays struggle with. It simply gives the most beautiful HLA data we have ever seen.” As part of this collaboration, Omixon developed assay-specific software, which gives scientists higher confidence in the results and the first phase is already underway with five additional labs being trained in the protocol developed by the Monos lab. Omixon and the participants intend to publish the results of the blind study in a leading peer-reviewed academic journal to facilitate confidence in the adoption of NGS for HLA genotyping among the wider clinical community.

The long-term objectives are clear to Dr. Berces, “This collaboration forms a key component of Omixon’s long term vision for HLA and immunogenetics. HLA will play an increasingly important role in disease and safety associations, and therapeutic selection in personalized medicine. With growing applications of HLA, the size of the HLA typing market will also grow substantially.” Continuous improvements to the assay and the software are also part of the long-term goal of this collaboration.

Visit PRWeb and GenomeWeb for more…