학술논문

Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
Document Type
article
Author
Gabor, AttilaTognetti, MarcoDriessen, AliceTanevski, JovanGuo, BaosenCao, WencaiShen, HeYu, ThomasChung, VerenaBodenmiller, BerndSaez‐Rodriguez, JulioPrusokas, AugustinasPrusokas, AlidivinasRetkute, RenataRajasekar, AnandRaman, KarthikSudhakar, MalvikaRengaswamy, RaghunathanShih, Edward SCKim, Min‐jeongCho, ChangjeKim, DohyangOh, HyejuHwang, JinseubJongtae, KimNam, YeongeunYoon, SanghooKwon, TaeyongLee, KyeongjunChaudhary, SarikaSharma, NehalBande, ShreyaCankut Cubuk, Gao Gao fan zhuGundogdu, PelinDopazo, JoaquinRian, KinzaLoucera, CarlosFalco, Matias MGarrido‐Rodriguez, MartinPeña‐Chilet, MariaChen, HuiyuanTuru, GaborHunyadi, LaszloMisak, AdamZhou, LishengJiang, XiaoqingZhang, PietaRai, AakanshaKutum, RintuRana, SadhnaSrinivasan, RajgopalPradhan, SwatantraLi, JamesBajic, VladimirVan Neste, ChristopheBarradas‐bautista, DidierAlbarade, Somayah AbdullahNikolskiy, IgorSinkala, MusalulaTran, DucNguyen, HungNguyen, TinWu, AlexanderDeMeo, BenjaminHie, BrianSingh, RohitLiu, JiweiChen, XueerSaiz, LeonorVilar, Jose MGQiu, PengGosain, AkashDhall, AnjaliBajaj, DineshKaur, HarpreetBagaria, KrishnaChauhan, MayankSharma, NeelamRaghava, GajendraPatiyal, SumeetHao, JianyePeng, JiajieNing, ShangyiMa, YiWei, ZhongyuAalto, AtteGoncalves, JorgeMombaerts, LaurentDai, XinnanZheng, JieMundra, PiyushkumarXu, FanWang, JieKant Singh, KrishnaLee, Mingyu
Source
Molecular Systems Biology. 17(10)
Subject
Cancer
Breast Cancer
1.1 Normal biological development and functioning
Underpinning research
Generic health relevance
Breast Neoplasms
Female
Humans
Machine Learning
Proteins
Signal Transduction
cell signaling
crowdsourcing
mass cytometry
predictive modeling
single cell
Single Cell Signaling in Breast Cancer DREAM Consortium members
Biochemistry and Cell Biology
Other Biological Sciences
Bioinformatics
Language
Abstract
Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi-signaling networks across cells and cell types, with important implications to understand and treat diseases such as cancer. These technologies are, however, limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organized the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry dataset, covering 36 markers in over 4,000 conditions totaling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time-course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data.