Artificial Intelligence Accelerated by Light

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cases where gene deletions cause moderate There are some limitations, however. humans, or that exhibit a distinct pattern of cell loss. The group named their technique CRISPR-LICHT is most suited to studies of early activity in humans14, could be a powerful way CRISPR-lineage tracing at cellular resolution development or cell proliferation. The cerebral of connecting genes to traits in the context of in heterogeneous tissue (CRISPR-LICHT). organoids in the current study were grown for human neural development. The researchers ranked the lineage-barcode 40 days, corresponding to development of depletion of the 173 genes thought to pose a the human brain early in the first trimester, so Adriana Cherskov and Nenad Sestan are in the risk of microcephaly, and examined the top neurons and glia that develop and mature later Department of Neuroscience, Yale School of 32 genes in further detail. They investigated were not considered. Using longer differentia- Medicine, New Haven, Connecticut 06510, USA. the role of these genes in regulating cell tion times would increase the turnaround time. e-mails: [email protected]; proliferation by using a mixing strategy, in Furthermore, current protocols for organoid [email protected] which they grew organoids from a combina- growth might activate cellular stress pathways, 10 1. Woods, C. G. Curr. Opin. Neurobiol. 14, 112–117 (2004). tion of control cells and cells that had been impairing cell-type specification and fidelity . 2. Dixon-Salazar, T. J. & Gleeson, J. G. Ann. NY Acad. Sci. genetically edited to lack the gene, and ana- Finally, not all of the cortex is the same, with 1214, 156–167 (2010). lysed the ratio of control to edited cells in the different regions having cell types and con- 3. Jayaraman, D., Bae, B.-I. & Walsh, C. A. Annu. Rev. Genom. Hum. Genet. 19, 177–200 (2018). fully grown organoids. Finding significantly nections that serve different functions. More- 4. Esk C. et al. Science 370, 935–941 (2020). reduced numbers of edited cells suggests that precise protocols would be required to model 5. Liao, B.-Y. & Zhang, J. Proc. Natl Acad. Sci. USA 105, 6987–6992 (2008). deletion of the gene causes reduced prolifer- this complexity and regionalization. 6. Eiraku, M. et al. Cell Stem Cell 3, 519–532 (2008). ation. Of the 32 genes studied, 25 were found Beyond clinical studies, the CRISPR-LICHT 7. Mariani, J. et al. Proc. Natl Acad. Sci. USA 109, 12770–12775 to be implicated in cell proliferation. platform could be applied to study the genetic (2012). 8. Gladwyn-Ng, I. et al. Nature Neurosci. 21, 63–71 (2018). Finally, Esk et al. focused on one particu- changes and mechanisms underlying the evo- 9. McConnell, M. J. et al. Science 356, eaal1641 (2017). lar gene of the set, which encodes immedi- lution of the healthy human brain. Evidence 10. Bhaduri, A. et al. Nature 578, 142–148 (2020). ate early response 3 interacting protein 1 indicates that the expansion and folding of 11. Heide, M. et al. Science 369, 546–550 (2020). 12. Fiddes, I. T. et al. Cell 173, 1356–1369 (2018). (IER3IP1). When cells were engineered to the human cortex depend on human-specific 13. Suzuki, I. K. et al. Cell 173, 1370–1384 (2018). lack this gene, the resulting organoids were properties of early neuronal development11–13. 14. Sousa, A. M. M., Meyer, K. A., Santpere, G., Gulden, F. O. & Sestan, N. Cell 170, 226–247 (2017). smaller than the controls. Analysis of orga- Using brain organoids to screen genes and noids lacking this gene revealed that it seems other DNA elements that are unique to This article was published online on 23 December 2020. to regulate the unfolded protein response — a cellular response to stress in an intracellular Information technology organelle called the endoplasmic reticulum that leads to reduced protein synthesis. Treat- ment of cells with a small molecule called Artificial intelligence the integrated stress response inhibitor, which restores protein synthesis, led to normal size and organization of neural progenitors in the accelerated by light organoids. These findings are particularly interesting because they tie the stress-in- Huaqiang Wu & Qionghai Dai duced unfolded protein response, which has previously been associated with Zika virus- The explosive growth of artificial intelligence calls for related microcephaly8, to a genetic cause of the rapidly increasing computing power. Two reported photonic disorder. The experiments highlight the enor- processors could meet these power requirements and mous potential of CRISPR-LICHT to investigate the mechanisms that underlie neurodevelop- revolutionize artificial-intelligence hardware. See p.44 & p.52 mental disorders. Although Esk and colleagues focused specif- ically on genes associated with microcephaly, Artificial intelligence (AI) is transforming performance. These networks perform com- their cost-effective and time-saving method various fields, such as clinical diagnosis, plex mathematical operations using many will be widely applicable to other neuro autonomous driving and speech translation. layers of interconnected artificial neurons3. developmental disorders. The Developmen- However, the quickly increasing volume of The fundamental operation that uses most of tal Brain Disorder Gene Database (go.nature. data in modern society poses great challenges the computational resources is called matrix– com/3mezn8d) lists about 600 genes whose for the electronic computing hardware used vector multiplication. deletion is associated with neurodevelopmen- in AI, in terms of both computing speed and Various efforts have been made to design tal disorders such as autism, schizophrenia power consumption. Such issues have become and implement specific electronic computing and epilepsy. These genes can now be screened a major bottleneck for AI. On pages 44 and 52, systems to accelerate processing in artificial by CRISPR-LICHT. respectively, Xu et al.1 and Feldmann et al.2 neural networks. In particular, considerable The approach could also be used to study report photonic processors that accelerate AI success has been achieved using custom chips genes that are under- or overexpressed in processing by harnessing the distinctive prop- known as application-specific integrated neurodevelopmental disorders, by adapt- erties of light. These demonstrations could circuits4, brain-inspired computing5 and ing it to modify, rather than eliminate, gene inspire a renaissance of optical computing. in-memory computing6, whereby processing expression. Furthermore, the dual-barcoding With the rise of AI, conventional electronic is performed in situ with an array of memory techniques of CRISPR-LICHT could be used to computing approaches are gradually reach- devices called memristors. create and track genetically distinct popula- ing their performance limits and lagging Electrons are the carriers of information in tions of cells, to model the effects of genetic behind the rapid growth of data available electronic computing, but photons have long variations among cells in the developing for processing. Among the various types been considered an alternative option. Because brain9. Finally, the approach could be used to of AI, artificial neural networks are widely the spectrum of light covers a wide range analyse genes associated with cancer. used for AI tasks because of their excellent of wavelengths, photons of many different

News & views wavelengths can be multiplexed (transmitted particular, they suggest that the processor the reported photonic processors have high in parallel) and modulated (altered in such a could be used in a hybrid optical–electronic computing power per unit area and potential way that they can carry information) simulta- framework, such as for in situ computations scalability, the all-optical computing scale (the neously without the optical signals interfering during optical-fibre communications. number of optical artificial neurons) remains with each other. This propagation of informa- Feldmann and colleagues independently small. Moreover, the energy efficiency is lim- tion at the speed of light results in minimal made an integrated photonic processor ited by the presence of computing elements time delays. Moreover, passive transmission (in that performs a convolution involving opti- that inherently absorb light and because elec- which no input power is required) aids ultralow cal signals that span two dimensions. The trical and optical signals frequently need to be power consumption7, and phase modulation device uses optical frequency combs in an interconverted. (whereby the quantum-mechanical phases of ‘in-memory’ computing architecture that is Another avenue of research is the devel- light waves are varied) enables light to be easily based on a phase-change material (a mater opment of advanced nonlinear integrated modulated and detected at frequencies greater ial that can switch between an amorphous photonic computing architectures, rather than 40 gigahertz (ref. 8). phase and a crystalline phase). The authors than one- or two-dimensional linear convo- In the past few decades, great success has fully parallelized the input data through wave- lutions. By integrating electronic circuits and been attained in optical-fibre communication. length multiplexing and conducted analogue thousands or millions of photonic processors However, it remains challenging to use matrix–vector multiplication using an array of into a suitable architecture, a hybrid optical– photons for computing, especially at a scale integrated cells of the phase-change material. electronic framework that takes advantage and performance level comparable to those Such a highly parallelized framework can of both photonic and electronic processors of state-of-the-art electronic processors. potentially process an entire image in a single could revolutionize AI hardware in the near This difficulty arises from a lack of suitable step and at high speed. Moreover, in principle, future. Such hardware would have important parallel-computing mechanisms, materials the system can be substantially scaled up using applications in areas such as communication, that permit high-speed nonlinear (complex) commercial manufacturing procedures and data-centre operation and cloud computing. responses of artificial neurons and scalable aid in situ machine learning in the near future. photonic devices for integration into comput- Because the convolution process involves Huaqiang Wu is at the Institute of ing hardware. passive transmission, the calculations of Microelectronics, Tsinghua University, Fortunately, developments over the past the photonic processing core can, in theory, Beijing 100084, China. Qionghai Dai is in few years in devices called optical frequency be performed at the speed of light and with the Department of Automation, Tsinghua combs9 brought new opportunities for inte- low power consumption. This ability would University, Beijing 100084, China. grated photonic processors. Optical fre- be extremely valuable for energy-intensive e-mails: [email protected]; quency combs are sets of light sources with applications, such as cloud computing. [email protected] emission spectra that consist of thousands Given the challenges facing conventional or millions of sharp spectral lines that are electronic computing approaches, it is exciting 1. Xu, X. et al. Nature 589, 44–51 (2021). 2. Feldmann, J. et al. Nature 589, 52–58 (2021). uniformly and closely spaced in frequency. to see the emergence of integrated photonics 3. LeCun, Y., Bengio, Y. & Hinton, G. Nature 521, 436–444 These devices have achieved substantial suc- as a potential successor to achieve unprece- (2015). cess in various fields, such as spectroscopy, dented performance for future computing 4. Silver, D. et al. Nature 550, 354–359 (2017). 5. Merolla, P. A. et al. Science 345, 668–673 (2014). optical-clock metrology and telecommunica- architectures. However, building a practi- 6. Sebastian, A., Le Gallo, M., Khaddam-Aljameh, R. & tion, and were recognized with the 2005 Nobel cal optical computer will require extensive Eleftheriou, E. Nature Nanotechnol. 15, 529–544 (2020). Prize in Physics. Optical frequency combs can interdisciplinary efforts and collaborations 7. Lin, X. et al. Science 361, 1004–1008 (2018). 9 8. Shen, Y. et al. Nature Photon. 11, 441–446 (2017). be integrated into a computer chip and used between researchers in materials science, 9. Stern, B., Ji, X., Okawachi, Y., Gaeta, A. L. & Lipson, M. as power-efficient energy sources for optical photonics, electronics and so on. Although Nature 562, 401–405 (2018). computing. This system is well suited for data parallelization by wavelength multiplexing. Epidemiology Xu and colleagues used such a set-up to produce a versatile integrated photonic processor. This device performs a type of matrix–vector multiplication known as a convolution for Big data and simple image-processing applications. The authors implemented an ingenious method to carry models to track COVID-19 out the convolution. They first used chro- matic dispersion — whereby the speed of Kevin C. Ma & Marc Lipsitch transmitted light depends on its wavelength — to produce different time delays for wave- Understanding the dynamics of SARS-CoV-2 infections could length-multiplexed optical signals. They then help to limit viral spread. Analysing mobile-phone data to track combined these signals along the dimension human contacts at different city venues offers a way to model associated with the wavelength of the light. By fully exploiting the wide range of photon infection risks and explain infection disparities. See p.82 wavelengths, Xu et al. achieved intrinsically parallel computing for different convolution operations. The optical-computing speed Behind the highly politicized disagreements which these goals are mutually reinforcing, was beyond ten trillion operations per second over COVID-19 control measures lies a widely and whether there is a trade-off between using a single processing core and was limited shared desire to return economic and social greater viral transmission and increased only by the data throughput. Another welcome life to sustainable levels as soon and for as long social and economic activity. The difficulty feature of this work is that the authors iden- as possible, while preserving health-care sys- in identifying control measures that are both tify the entry point of their photonic convo- tems and minimizing severe illness and death. effective and minimally disruptive motivates lution processor in practical applications. In The main arguments are about the extent to the search for new approaches to modelling