Researchers from OICR and other institutions have created a new software program called EAGLE that mines data to understand the interactions between a person’s environment and their genetics. The tool has far-reaching uses, including oncology, and can provide researchers and clinicians with important information that can help personalize treatments for patients.
To learn more we spoke to Dr. Hillary Edgington, a Postdoctoral Fellow in OICR’s Informatics technology platform, which is led by Dr. Lincoln Stein. Edgington and her collaborators recently shared their research in the journal Nature Methods.
What was reported in your recent article?
One of the most important goals in biological research is to understand the ways that our genes can be impacted by the environment around us. The activity of genes can change due to a number of external factors from medication use to air pollution. This study introduces a new software tool called EAGLE to investigate how interactions between a person’s genotype and environmental exposures affect the way his or her genes are expressed.
What is unique about EAGLE?
EAGLE takes advantage of the fact that sometimes the two copies of a gene are unequally expressed, which allows us to compare small differences in those two copies within an individual where they operate in the same environmental conditions. This tool was shown to improve, in both power and accuracy, on detecting associations over standard interaction testing methods. Using EAGLE to test for interactions in two large cohorts (the Depression Genes and Networks study cohort and CARTaGENE) revealed significant associations between gene expression and environmental variables, including depression, exercise, blood pressure medication use and body mass index. This information is critical in advancing personalized healthcare initiatives, as it gives researchers and clinicians information with which to predict an individual’s health risks based on their unique genomic profile and lifestyle factors.
How can these findings be used in the area of cancer?
EAGLE is a tool that can be applied to data from any source. The information gleaned from the application of EAGLE to data provided by cancer patients – including testing for interactions between patients’ specific mutational profiles and exposures such as therapeutic treatments, the microenvironment of the tumour, or properties of the immune system – could help clinicians make more accurate predictions about individual patients’ prognoses and therapeutic options in the future.
What challenges did you and your collaborators face while creating EAGLE?
One of the main challenges with developing any new method is making sure that the results will be consistent across different groups of individuals. It is critical to perform tests in different groups in order to make sure that there is replication of any findings. For this reason, collaboration between different research groups is critical, and this is what brought the groups from OICR and Stanford University together on this project. At OICR we were able to use the resources that we have through the CARTaGENE cohort to perform a replication study. It showed that the associations EAGLE detected in the Depression Genes and Networks cohort are consistent across populations.
What are the next steps planned with this research project?
We will be able to use EAGLE in many future projects as a way to discover previously unknown interactions between any environmental variable of interest and the regulation of genes. As a follow-up to this study we may look more specifically at the gene-environment associations we observed in order to determine what the mechanism is that causes differences in gene expression.
Watafiti kutoka OICR na taasisi nyingine wameunda programu mpya ya programu inayoitwa EAGLE ambayo inachimba data ili kuelewa mwingiliano kati ya mazingira ya mtu na maumbile yake. Programu hiyo ina matumizi mengi, ikiwa ni pamoja na oncology, na inaweza kutoa watafiti na madaktari habari muhimu ambayo inaweza kusaidia kuboresha matibabu kwa wagonjwa. Ili kujua zaidi, tulizungumza na Dk Hillary Edgington, mwanachama wa Postdoctoral katika jukwaa la teknolojia ya OICR, ambalo linaongozwa na Dk Lincoln Stein. Edgington na washirika wake hivi karibuni walishiriki utafiti wao katika jarida la Nature Methods. Ni nini kilichoripotiwa katika makala yenu ya hivi karibuni? Moja ya malengo muhimu zaidi katika utafiti wa kibiolojia ni kuelewa njia ambazo jeni zetu zinaweza kuathiriwa na mazingira yanayotuzunguka. Utendaji wa chembe za urithi waweza kubadilika kwa sababu ya mambo kadhaa ya nje kuanzia matumizi ya dawa hadi uchafuzi wa hewa. Utafiti huu unaanzisha chombo kipya cha programu kinachoitwa EAGLE kuchunguza jinsi mwingiliano kati ya genotype ya mtu na mfiduo wa mazingira unavyoathiri njia ambayo jeni zake zinaonyeshwa. Ni nini kipekee kuhusu EAGLE? EAGLE hutumia ukweli kwamba wakati mwingine nakala mbili za jeni huonyeshwa kwa njia isiyo sawa, ambayo inaruhusu kulinganisha tofauti ndogo katika nakala hizo mbili ndani ya mtu mmoja ambapo zinafanya kazi katika hali sawa za mazingira. Chombo hiki ilionyeshwa kuboresha, katika nguvu na usahihi, juu ya kugundua mashirika juu ya mbinu za kawaida za kupima mwingiliano. Kwa kutumia EAGLE kupima mwingiliano katika makundi mawili makubwa (kikundi cha utafiti wa Depression Genes and Networks na CARTAGENE) ilifunua ushirika muhimu kati ya usemi wa jeni na vigezo vya mazingira, pamoja na unyogovu, mazoezi, matumizi ya dawa za shinikizo la damu na index ya wingi wa mwili. Habari hii ni muhimu katika kuendeleza mipango ya huduma ya afya ya kibinafsi, kwani inatoa watafiti na madaktari habari ambayo inaweza kutabiri hatari za afya za mtu binafsi kulingana na wasifu wao wa kipekee wa genomu na sababu za mtindo wa maisha. Ugunduzi huu unaweza kutumikaje katika eneo la kansa? EAGLE ni chombo ambacho kinaweza kutumika kwa data kutoka chanzo chochote. Habari zilizopatikana kutoka kwa matumizi ya EAGLE kwa data zinazotolewa na wagonjwa wa kansa - ikiwa ni pamoja na kupima kwa mwingiliano kati ya wagonjwa - maelezo maalum ya mabadiliko na mfiduo kama vile matibabu ya matibabu, mazingira madogo ya uvimbe, au mali ya mfumo wa kinga - inaweza kusaidia madaktari kufanya utabiri sahihi zaidi juu ya wagonjwa wa mtu binafsi na chaguzi za matibabu katika siku zijazo. Ni changamoto gani ambazo wewe na wenzako mlikabili wakati wa kuunda EAGLE? Moja ya changamoto kuu katika kuendeleza mbinu yoyote mpya ni kuhakikisha kwamba matokeo itakuwa thabiti katika makundi tofauti ya watu. Ni muhimu kufanya vipimo katika vikundi tofauti ili kuhakikisha kwamba kuna replica ya matokeo yoyote. Kwa sababu hii, ushirikiano kati ya vikundi tofauti vya utafiti ni muhimu, na hii ndiyo iliyoleta vikundi kutoka OICR na Chuo Kikuu cha Stanford pamoja kwenye mradi huu. Katika OICR, tumeweza kutumia rasilimali ambazo tuna kupitia kundi la CARTAGENE kufanya utafiti wa kuiga. Utafiti huo ulionyesha kwamba uhusiano uliopatikana katika kundi la watu wa Depression Genes and Networks ni sawa katika idadi ya watu. Hatua zifuatazo zimepangwa kwa mradi huu wa utafiti? "Tutaweza kutumia EAGLE katika miradi mingi ya baadaye kama njia ya kugundua mwingiliano ambao haujulikani hapo awali kati ya mabadiliko yoyote ya mazingira ya maslahi na udhibiti wa jeni. """ Kwa kuzingatia utafiti huu, tunaweza kuangalia kwa undani zaidi ushirika wa jeni na mazingira tuliyoyaona ili kuamua ni nini utaratibu unaosababisha tofauti katika usemi wa jeni.