181 genome regions of scientific interest identified in breast cancer cells thanks to Genigma app

By June 22, 2022June 28th, 2022CRG

• This month heralded the conclusion of the #GenigmaChallenge, the first participative experiment to analyse the human genome through a mobile phone app, GENIGMA, in which more than 39,000 people from 154 countries participated.
• 600,287 solutions have been gathered in a matter of 20 weeks and 181 Eureka! regions, areas of the genome of interest in breast cancer research, have been identified.
• The player community dedicated 19,485 hours to scanning, on a step-by-step basis, the 23 chromosomes loaded into the app by the scientific team.
• As of now, it will be possible to play with fragments of the genome of the Eureka! zones identified during the weeks the #GenigmaChallenge ran. In this way, the scientific team will try to test whether it is possible to progress in the analysis of the arrangement of these fragments to a higher level of resolution.

In the course of 139 days, the GENIGMA video game for iOS and Android, created by a research team from the Centro Nacional de Análisis Genómico (CNAG-CRG), part of the BIST centre CRG, threw down the #GenigmaChallenge gauntlet to players from all over the world to solve puzzles to contribute to furthering progress in cancer research. The objective was to collaborate to identify the chromosomal regions affected by anomalies in T-47D breast cancer cell culture. These are the most commonly used cells by the worldwide scientific community in research into this type of cancer.

Cell cultures are a cornerstone of modern biology and have been used to discover vaccines, chemotherapy for cancer or in vitro fertilisation”, explains the ICREA research Professor Marc A. Marti-Renom, a member of both the CRG and the CNAG-CRG, and whose research underpins GENIGMA. “Nevertheless, we still lack detailed knowledge of how the genome of each one of these cultures is organised and this continues to limit scientific progress. This experiment was designed to test whether it is possible to identify areas of interest in the genome of these cells quickly and collaboratively.”

20 weeks with the #GenigmaChallenge

Based on the real data obtained in the laboratory with the T-47D breast-cancer cell culture, the scientific team divided all the DNA into small fragments and created 5,442 puzzles to be analysed by the community of players.

Every week, puzzles of 8, 10, 12 and up to 15 pieces were uploaded to GENIGMA for analysis using human logic and with the aid of virtual tools integrated into the game.

Genigma has more than 5,000 puzzles, which contain parts of the genome of 100,000 base pairs of the 3,000,000,000 that make up our genome. The challenge of putting them in order could only be accomplished by dividing the “big puzzle” into small parts that each player could solve”, explains Marc A. Marti-Renom, in reference to the “divide and conquer” strategy implemented by the GENIGMA team when they designed the game.

In 20 weeks, more than 44,000 people from 154 countries have downloaded the game and provided more than 600,000 solutions”, explains Elisabetta Broglio, the CRG’s citizen science facilitator. “With the help of the social media and the traditional media, we gradually assembled a huge team of volunteers from all over the world who contributed to this research in their free time. It is an unprecedented challenge in this field and we are truly impressed with the degree of participation. Throughout the experiment, we kept the community posted on the achievements obtained on a weekly basis through the genigmagame.app app, the app’s internal messaging system, Twitter, Facebook and Instagram. We also interacted with the community, tweaking certain features of the app, and we also prepared extra content to handle queries and to maintain interest in the project.”

The experiment lasted four and a half months, over the course of which the app was updated on five occasions, bringing in improvements suggested by the citizens (in the tutorial, the scoring system, the viewing of individual achievements and also including new scientific dissemination cards).

When we launched the game, we asked the players to play a minimum of 50 games to participate in the experiment. Nevertheless, this minimum was more than surpassed in many cases. Moreover, some people have been playing and supporting the project right to the end and have also participated in disseminating and sharing their playing strategies in order to get the highest number of people possible to opt into this collective effort. Their involvement was also decisive in the success of the project”, says Broglio.

Chromosomal regions of great research interest

Over the 139 days that the #GenigmaChallenge lasted, the puzzles in which at least 40 different players managed to beat the record score indicated in the game were tagged as Eureka! regions. All in all, in the entire genome of these cells, 181 of these regions regarded as being of high scientific interest were identified, since they show that the genome sequence could be affected by chromosomal rearrangements if we compare it to the sequences of the non-cancerous cells. The regions in which the proposed record was not beaten, also solved by consensus, are probably regions with a similar arrangement to that of their homologous regions in healthy cells, which implies that they would not be affected by any chromosomal alteration.

Now that the analysis of the entire genome has been completed, the Eureka! regions identified will be analysed in detail by our scientific team”, states Marc A. Marti-Renom. “Once these results have been analysed, we will consider the possibility of using GENIGMA to analyse other types of cancer.”

Learn more on the CRG website.