EuResist
Encyclopedia
EuResist is an international project designed to improve the treatment of HIV
patients by developing a computerized system that can recommend optimal treatment based on the patient’s clinical and genomic data.
The project is part of the Virtual Physiological Human
framework, funded by the European Commission
. It started in 2006 with the formation of a consortium of several research institutes and hospitals in Europe
and Israel
. The consortium completed its commitment to the European Commission
near the end of 2008, at which time the system became available online. A non-profit organization was consequently established by the main partners to maintain and improve the system.
In 2009, the EuResist project was named as a Computerworld honors program laureate.
is a disease caused by the HIV
retrovirus
, which progressively reduces the effectiveness of the immune system
, leading to infections and ultimately death
.
More than 30 different drugs exist for treating HIV patients. Antiretroviral drugs can disrupt the virus’s replication process causing its numbers to decrease dramatically. While the virus cannot be eradicated completely, in small numbers it is harmless. Usually a patient is given a combination of three or four drugs, a treatment known as highly active antiretroviral therapy, or HAART. The main reason such a treatment might fail is the development of mutated strands of the virus, resistant to one or more of the prescribed drugs.
Thus an important consideration when choosing treatment for a patient is to prescribe those drugs to which the particular patient’s virus strands are most susceptible. One way to achieve that is to extract virus samples from the patient’s blood and test them against all possible drugs. Since this process is lengthy and costly, computerized systems have been developed to predict virus resistance based on its genotype. The treating physician samples virus genotype sequences from the patient’s blood and provides this data to a computerized system. The system then responds with drug recommendations.
Such systems are limited in accuracy, depending on the amount of data used for their creation, its quality and the richness of mathematical models used for the actual prediction. Prior to EuResist, such systems had several common characteristics that negatively impacted their accuracy:
data (clinical and genomic records of real treatments of HIV patients and their consequences), and by using an array of prediction models instead of just one.
The database was created by merging local databases of various clinics across Europe. This database is thought to be the largest of its kind in the world.
For each patient, it includes various personal and demographic details such as gender, age, country of origin, genomic sequencing of HIV found in the patient’s blood, records of the drugs prescribed, and the changes in the amount of virus in the blood following these treatments.
This data was used to train an array of prediction models, created by using various contemporary machine learning
techniques, among them Bayesian networks, logistic regression
, and others.
A web interface allows physicians to specify patients' clinical and genomic data. This data is sent to the prediction engines, and the combined response, which is displayed to the physician, includes various suggested treatments and a prediction of their effect on the amount of HIV in the blood.
The EuResist system was tested and compared with its predecessors by feeding it with historical data on patients for which treatment results are known. The developers of EuResist, who conducted this test, reported an improved performance over the previous state-of-the-art system.
as part of the Virtual Physiological Human
FP-6 framework. The partners of this consortium were:
The consortium completed its commitment to the European Union
in late 2008, at which time the EuResist system became available on line.
The first five partners mentioned above continued to form a non-profit organization that maintains the system, expands the database with new clinical and genomical records and updates the prediction engines accordingly. As of mid-2010, an average of 600 queries are submitted to the EuResist system every quarter.
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
patients by developing a computerized system that can recommend optimal treatment based on the patient’s clinical and genomic data.
The project is part of the Virtual Physiological Human
Virtual Physiological Human
The Virtual Physiological Human is a methodological and technological framework that, once established, will enable collaborative investigation of the human body as a single complex system...
framework, funded by the European Commission
European Commission
The European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....
. It started in 2006 with the formation of a consortium of several research institutes and hospitals in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
and Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
. The consortium completed its commitment to the European Commission
European Commission
The European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....
near the end of 2008, at which time the system became available online. A non-profit organization was consequently established by the main partners to maintain and improve the system.
In 2009, the EuResist project was named as a Computerworld honors program laureate.
Background
AIDSAIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
is a disease caused by the HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
, which progressively reduces the effectiveness of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, leading to infections and ultimately death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
.
More than 30 different drugs exist for treating HIV patients. Antiretroviral drugs can disrupt the virus’s replication process causing its numbers to decrease dramatically. While the virus cannot be eradicated completely, in small numbers it is harmless. Usually a patient is given a combination of three or four drugs, a treatment known as highly active antiretroviral therapy, or HAART. The main reason such a treatment might fail is the development of mutated strands of the virus, resistant to one or more of the prescribed drugs.
Thus an important consideration when choosing treatment for a patient is to prescribe those drugs to which the particular patient’s virus strands are most susceptible. One way to achieve that is to extract virus samples from the patient’s blood and test them against all possible drugs. Since this process is lengthy and costly, computerized systems have been developed to predict virus resistance based on its genotype. The treating physician samples virus genotype sequences from the patient’s blood and provides this data to a computerized system. The system then responds with drug recommendations.
Such systems are limited in accuracy, depending on the amount of data used for their creation, its quality and the richness of mathematical models used for the actual prediction. Prior to EuResist, such systems had several common characteristics that negatively impacted their accuracy:
- The amount of data used for creating the system was relatively small
- This data was in vitroIn vitroIn vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
data: laboratory measures of the resistance of various strands of HIV to individual drugs. Such data is known to be inaccurate because laboratory tests do not simulate exactly the processes of a living organism, and since resistance to individual drugs does not accurately predict the resistance to a combination of drugs. - They used a relatively simple mathematical prediction model
EuResist overview
EuResist sought to create a more accurate HIV treatment prediction system by collecting a large database of in vivoIn vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
data (clinical and genomic records of real treatments of HIV patients and their consequences), and by using an array of prediction models instead of just one.
The database was created by merging local databases of various clinics across Europe. This database is thought to be the largest of its kind in the world.
For each patient, it includes various personal and demographic details such as gender, age, country of origin, genomic sequencing of HIV found in the patient’s blood, records of the drugs prescribed, and the changes in the amount of virus in the blood following these treatments.
This data was used to train an array of prediction models, created by using various contemporary machine learning
Machine learning
Machine learning, a branch of artificial intelligence, is a scientific discipline concerned with the design and development of algorithms that allow computers to evolve behaviors based on empirical data, such as from sensor data or databases...
techniques, among them Bayesian networks, logistic regression
Logistic regression
In statistics, logistic regression is used for prediction of the probability of occurrence of an event by fitting data to a logit function logistic curve. It is a generalized linear model used for binomial regression...
, and others.
A web interface allows physicians to specify patients' clinical and genomic data. This data is sent to the prediction engines, and the combined response, which is displayed to the physician, includes various suggested treatments and a prediction of their effect on the amount of HIV in the blood.
The EuResist system was tested and compared with its predecessors by feeding it with historical data on patients for which treatment results are known. The developers of EuResist, who conducted this test, reported an improved performance over the previous state-of-the-art system.
History
EuResist started in 2006 as a consortium funded by the European UnionEuropean Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
as part of the Virtual Physiological Human
Virtual Physiological Human
The Virtual Physiological Human is a methodological and technological framework that, once established, will enable collaborative investigation of the human body as a single complex system...
FP-6 framework. The partners of this consortium were:
- Informa S.r.l. (ItalyItalyItaly , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
) - University of SienaUniversity of SienaThe University of Siena in Siena, Tuscany is one of the oldest and first publicly funded universities in Italy. Originally called Studium Senese, the University of Siena was founded in 1240. The University has around 20,000 students, nearly half of Siena's total population of around 54,000...
(ItalyItalyItaly , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
) - Karolinska InstitutetKarolinska InstitutetKarolinska institutet is a medical university in Solna within the Stockholm urban area, Sweden, and one of Europe's largest medical universities...
(SwedenSwedenSweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
) - Universitätsklinikum Koeln (GermanyGermanyGermany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
) - Max Planck Institute for Informatics (GermanyGermanyGermany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
) - IBM Haifa Research LaboratoryIBM Haifa Research LaboratoryIBM Haifa Research Laboratory is located in Haifa, Israel. It is one of several IBM R&D Labs in Israel.IBM Haifa Research Laboratory handles projects in the spheres of cloud computing , healthcare and life sciences, verification technologies , multimedia, event processing , information retrieval...
(IsraelIsraelThe State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
) - MTA KFKI Reszecske-ES Magfizikai KutatoIntezet (HungaryHungaryHungary , officially the Republic of Hungary , is a landlocked country in Central Europe. It is situated in the Carpathian Basin and is bordered by Slovakia to the north, Ukraine and Romania to the east, Serbia and Croatia to the south, Slovenia to the southwest and Austria to the west. The...
) - Kingston UniversityKingston UniversityKingston University is a public research university located in Kingston upon Thames, southwest London, United Kingdom. It was originally founded in 1899 as Kingston Technical Institute, a polytechnic, and became a university in 1992....
(United KingdomUnited KingdomThe United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
)
The consortium completed its commitment to the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
in late 2008, at which time the EuResist system became available on line.
The first five partners mentioned above continued to form a non-profit organization that maintains the system, expands the database with new clinical and genomical records and updates the prediction engines accordingly. As of mid-2010, an average of 600 queries are submitted to the EuResist system every quarter.