Image: Skin cancer cells – Squamous cell carcinoma, NIH Image Gallery via Flickr Attribution-NonCommercial 2.0 Generic (CC BY-NC 2.0)
In this episode we’re digging into some of the mysteries around what’s often seen as the ultimate genetic disease: cancer.
We talk to Phil Jones at the Sanger Institute in Cambridge to unpack his latest research showing that low doses of X-rays – similar to what someone might receive from a few CT scans – can trigger the growth of potentially cancerous cells. And we sit down with Steve Elledge from Harvard Medical School to hear how he and his team are using their Cancer Research UK Grand Challenge Award to understand why tumours tend to arise in some tissues and not others. Plus, the evolutionary genetics of rats leaving a sinking ship.
If you enjoy the show, please do rate and review and spread the word. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com
Heinrich Reichert, Professor Emeritus at the University of Basel, Switzerland, passed away on the 13th of June 2019 after a prolonged illness. Heinrich described himself as ‘a hedonist when it came to science’ because he said it gave him great pleasure. It was this quality that made working with Heinrich thrilling and deeply fulfilling. Heinrich’s long and versatile career spanned the breadth of neuroscience – from development, to evolution and behaviour. In his passing we have lost not just an astute scientist, but also an impassioned educator and an adventurer of science.
Heinrich in Veerapura, Karnataka, India in 2014.
Heinrich grew up in Southern California, to where his parents had moved from Austria. He did his schooling there, but moved back to Europe to study Physics, Biology and Chemistry at the University of Karlsruhe, before doing his Masters at the neighbouring University of Freiburg. These were stimulating years for Heinrich. Inspired by Seymour Benzer’s work on genes and behaviour, he and colleagues established a behavioural paradigm for aversive learning in the fruit fly Drosophila – versions of this assay are standard in many laboratories today (Spatz et al., 1974). He continued on at Freiburg for his PhD in this productive period and collaborated extensively to combine electrophysiological recordings, genetics and behavioural approaches to understand the sensitivities of the photoreceptor neurons in Drosophila. These were also some of the rare years in recent history when it was possible to travel relatively easily from Europe to India by road. So, throwing life and science in a heady mix, Heinrich took a backpacking holiday from southwestern Germany, through Turkey, Iran, Afghanistan and Pakistan all the way into India in the middle of his PhD. Despite this long sojourn, he completed his PhD with three papers on visual perception and learning in Drosophila (Bicker and Reichert, 1978; Hu et al., 1978; Reichert and Bicker, 1979).
Heinrich was then on the lookout for new adventures. Jeffery Wine’s lab, in balmy Stanford, and the electrophysiologically accessible neurons of the crayfish caught his attention. How do nervous systems generate the different components of a behaviour in an orderly fashion? Heinrich decided to tackle this question in the crayfish escape response and spent three intense years unravelling the circuitry underlying it. Crayfish escape threatening stimuli by a near-instantaneous flick of the tail followed by a rapid burst of backward swimming. The initial flick is mediated by the giant fibre neurons and the swimming by a central pattern generator composed of non-giant fibre neurons. Combining direct electrical stimulation of the giant neurons with tactile stimulation of the crayfish in various ways, Heinrich and Wine showed that activation of the giant fibres did not initiate swimming. This ruled out the possibility that an early circuit (giant neurons) activated the later circuit (the central pattern generator). They went on to show that the same sensory stimulus activates both the giant fibre and the non-giant fibre circuits, but with different latencies, allowing the robustly ordered sequence of events that constitutes the stereotypical escape response (Reichert and Wine, 1982, 1983; Reichert et al., 1981, 1982). During this time, Heinrich also made his initial foray into insect flight in a collaboration with Mel Robertson at the University of Alberta in Canada. Together, they identified segmentally homologous interneurons in the locust that were active during flight and argued that this segmental homology reflected an appendage-like evolutionary origin of the wings (the contrary idea was that wings were an extension of the thorax) (Robertson et al., 1982).
Even before he completed his time at Stanford, Heinrich was offered an assistant professorship in the Zoological Institute at the University of Basel, Switzerland. When he got there, he dove straight into solving the circuitry of locust flight, much like he had the crayfish escape response in Stanford. In Basel, his group shifted organisms, but the central questions remained the same – how do interneurons integrate sensory inputs to modulate motor outputs? Over the period of his habilitation (qualification as a Professor) at Basel, Heinrich’s group made important contributions and published steadily – a salt-and-pepper mix of crayfish and locust stories around this idea.
He then moved to the University of Geneva where he found himself facing a new challenge. In Basel, Heinrich had been teaching undergraduate courses in German – a language he was fluent in. He now had to teach the same courses in French – a language he barely knew! But Heinrich had an uncanny flair for teaching. He could effortlessly distil complex ideas and weave them into conversational language. So, teaching in any language came easily to him. By this time, Heinrich was married to Dominique, herself a scientist, whose first language was French. In their first year of marriage, it was Dominique who helped Heinrich translate all his neurobiology lectures into French.
In 1991, Heinrich and Dominique moved back to Basel, where he was appointed an Associate Professor. This period saw a shift in Heinrich’s science. An underlying thread in his work had been the question of evolution, and of how neural circuitry was established during development. So, in Basel, Heinrich’s group began to look at the developmental origins of muscles and the nervous system in the grasshopper embryo. But it was soon clear that the grasshopper was not appropriate for this – this problem needed to be tackled in Drosophila. The way Heinrich told it, he only had a passive role to play in this decision – he was away on holiday, and when he came back, Drosophila had been smuggled into the lab. This was largely modesty. While Heinrich was certainly the sort of mentor who nurtured creative, independent pursuits from people in his group, he was also keenly aware of the workhorse that was Drosophila. Besides, there was a revolution underway. Following work by Michael Bate in the grasshopper, Corey Goodman and colleagues were beginning to look at the establishment of neural circuits during development and demonstrating the striking similarity in the ground-plan of grasshopper and Drosophila nervous systems. What was more, they were showing how genes coding for cell-surface proteins, transcription factors and signalling molecules were orchestrating its precise assembly. In Basel, Heinrich took this same approach and applied it to the central brain – a far more complex part of the nervous system that was, for all practical purposes, uncharted. But he stretched the argument further. If the circuits were evolutionarily conserved, maybe the genes that built them were too. Over the next few years, Heinrich’s group showed that this was indeed the case. You could swap the coding sequences of genes between species as far removed as Drosophila, mouse, human and even corals and achieve functional replacements – in most cases, and for the most part (Nagao et al., 1998). The implications of this are deep: if the circuits are conserved, and so are the genes, it would suggest that these vastly different extant nervous systems shared common evolutionary origins.
Heinrich’s second and far longer association with India came at this point – though it wasn’t Heinrich himself who initiated it. Robert Lichtneckert, who was doing his PhD with Heinrich at the time, was looking at the early embryonic patterning gene empty spiracles (ems) in the development of central brain when he stumbled into the olfactory circuit. ems seemed to be involved in both the central and peripheral neurons of the olfactory circuit – a system whose development Veronica Rodrigues had been studying in Mumbai. Lichtneckert wrote to Veronica, and so began a collaboration that lasted beyond ems and the olfactory system, beyond Veronica’s life, and even beyond Drosophila biology. Veronica fell ill shortly after this. It was to the credit of both Heinrich and Veronica that the science on which Robert Lichtneckert, Beate Hartmann, Abhijit Das and one of us (S.S.) collaborated continued seamlessly. Heinrich would visit the National Centre for Biological Sciences – Tata Institute for Fundamental Research (NCBS-TIFR) in Bangalore (where Veronica had since moved) twice, sometimes three times, a year for prolonged periods. He had become an integral part of the community. When Veronica passed away two years later, Heinrich became the adopted co-mentor of many of Veronica’s PhD students and he generously took them on. He naturally connected with students, which made his presence on campus invaluable – and not just for Veronica’s students. It was a common sight to see Heinrich in the bustling, sunny NCBS canteen, surrounded by students from different labs, sharing meals and science alike. Working with him was an absolute pleasure – he brought clarity to complex data and let the path ahead emerge from there. He was generous with his time and his intellect and met with everyone and anyone who wanted to discuss their work with him, without making any demands.
In Bangalore, Heinrich’s office was across from that of K. S. Krishnan, a cell biologist of the synapse and an Emeritus Professor at NCBS-TIFR. The two shared a common love for nature, particularly the ocean. Krishnan, an avid birder, was running an extraordinary project on isolating and characterising the diverse peptides that constitute the venom cocktail of marine cone snail species from coastal India; Heinrich was an avid scuba diver – a ‘birdwatcher of fish’, if you will. For decades he had been diving regularly in the Maldives and the Red Sea. In fact, for many years Heinrich, with others in his lab who were also certified divers, ran a marine biology course that took students to the Maldives to monitor coral reef ecosystems, looking particularly at the effect of and recovery after photobleaching. He also organised and taught two experimental marine biology courses at the marine stations in Roscoff and Banyuls in France every year, and neurobiology courses in Trieste and Cambodia. Krishnan and Heinrich’s common interest sparked a much larger project for India – a proposal for a new marine biology institute. Unfortunately, Krishnan passed away quite suddenly in 2014. But Heinrich threw all his efforts behind this idea. For two years, the Swiss man became part of an Indian delegation to establish formal collaborations with the French Centre National de la Recherche Scientifique (CNRS) and Université Pierre et Marie Curie (UPMC) and their three marine stations in Roscoff, Banyuls and Villefranche. He also travelled extensively within India and explored its islands to assess ideal locations for this new Indian marine institute. As India now considers budgetary allocations for this proposal, we owe Heinrich deeply for his generous, unselfish and tireless support of it.
Heinrich’s passing is a tremendous loss to developmental neuroscience. In the last few years before his retirement in 2015, his lab had begun to systematically take apart how the brain was built – in modules constituted by stem cells and their lineages. They were examining the genes that contributed to the identities of these stem cells, and therefore to the establishment of circuitry in the brain, as well as how faults in this programme could result in disease states such as in cancer. His science over the years constitutes a body of work that has greatly advanced our understanding of the brain, its construction and function. He has written textbooks in English and German that are considered essential reading. But Heinrich’s passing will be a loss to science for much more than that. In the current research environment that places high demands on the proxies of academic success, Heinrich exemplified success without dwelling on such proxies. As a mentor, this stripped the experience of science down to why we pursue it in the first case – the desire to understand something. As a collaborator, this meant a committed, unguarded pursuit of a common goal. Heinrich was a true intellect, a Renaissance human of the 21st century. His approach to science bore the same quality as his appreciation of music, literature, art, languages, or even cuisines. Yet he had no pomp and spoke only of what others did, never placing his own contributions at the centre. He was as willing to engage in discussions with students as he was with stalwarts; he equally appreciated quality street food of questionable provenance as he did fine dining; and he was always ready to roll up his sleeves to get something done. Heinrich will be sorely missed by developmental biologists and his friends alike. We who have benefited so much from his generosity and caring mentorship now have the enormous task to pass on this culture of science that he so carefully cultivated.
Heinrich is survived by Dominique and their three sons, Thomas, Marc and Paul.
Acknowledgements
We are grateful to Dominique Reichert, John Y. Kuwada, Michael Bate and Ajay Krishnan for their comments. We thank Sachin Chanchani for the photograph.
Research Assistant I – Investigating Microbial Protein Evolution with Functional Genomics
Position Summary: The Paul Lab at the MBL seeks a highly motivated individual to join the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution as a Research Assistant (Level I). The successful candidate will be responsible for carrying out routine laboratory work as outlined below. Our research group is looking at the processes that diversify microbial genes, to better understand the functional significance of protein variation in cells and viruses from a variety of biomes. This is a year-round, full time, non-exempt position.
Additional Information: The primary aim of the position is to maintain the molecular lab facilities and to assist in developing genetic experiments with bacteria/archaea primarily derived from marine and freshwater ecosystems. Responsibilities will include establishing and monitoring cell cultures, maintaining lab equipment, ordering lab supplies, and conducting basic molecular experiments.
Basic Qualifications: A Bachelor’s degree in biology, molecular biology or a related discipline is required. This position requires an independent, organized, and self-motivated individual with strong problem-solving skills and the ability to multitask. Prior experience in a research lab and applying basic molecular biology techniques is required. Excellent written, verbal, and interpersonal skills; attention to detail; and a strong work ethic are essential. Position level and salary will depend upon education and experience.
Preferred Qualifications: The ideal candidate will have prior experience with nucleic acid purification, PCR, and maintaining (bacterial/archaeal) cell cultures. An understanding of basic molecular biology concepts is important.
Physical Requirements: Minimal exposure to biohazardous chemicals. Occasional lifting of heavy objects.
Instructions:
Please apply on the MBL website and provide the following required documents: coverletter, resume/CV, copies of most recent transcripts(unofficial isacceptable), and contact details of 3 references. No request for reference letters at this time.
By decoding the genetic mechanisms that control the neurons of the visual system, researchers at UNIGE are unveiling the first steps in the construction of vision, paving the way for regenerative eye medicine. A Press Release from the University of Geneva.
How is the retina formed? And how do neurons differentiate to become individual components of the visual system? By focusing on the early stages of this complex process, researchers at the University of Geneva (UNIGE), Switzerland, in collaboration with the École Polytechnique Fédérale de Lausanne (EPFL), have identified the genetic programmes governing the birth of different types of retinal cells and their capacity to wire to the correct part of the brain, where they transmit visual information. In addition, the discovery of several genes regulating nerve growth allows for the possibility of a boost to optic nerve regeneration in the event of neurodegenerative disease. These results can be discovered in the journal Development.
The visual system of mammals is composed of different types of neurons, each of which must find its place in the brain to enable it to transform stimuli received by the eye into images. There are photoreceptors, which detect light, optic nerve neurons, which send information to the brain, cortical neurons, which form images, or interneurons, which make connections between other cells. Though not yet differentiated in the early stages of embryonic development, these neurons are all produced by progenitor cells that, are capable of giving rise to different categories of specialized neurons. To better understand the exact course of this mechanism and identify the genes at work during retinal construction, researchers studied the dynamics of gene expression in individual cells. “To monitor gene activity in cells and understand the early specification of retinal neurons, we sequenced more than 6,000 cells during retinal development and conducted large-scale bioinformatic analyses,” explains Quentin Lo Giudice, PhD student in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine and first author of this article.
Photoreceptors cells responsible for colour vision. By sequencing one cell at a time, the researchers identified a gene (Rbp4) present in a small number of cells (in green). In purple, photoreceptors in which the Rbp4 gene is not activated.
Mapping a system under construction
In collaboration with Gioele La Manno and Marion Leleu of EPFL, the researchers studied progenitor’s behaviour during the cell cycle as well as during their progressive differentiation. The scientists then mapped very accurately the different cell types of the developing retina and the genetic changes that occur during the early stages of this process. “Beyond their “age”—that is, when they were generated during their embryonic life—the diversity of neurons stems from their position in the retina, which predestines them for a specific target in the brain,” explains Pierre Fabre, senior researcher in the Department of Basic Neurosciences at the UNIGE Faculty of Medicine, who directed this work. “In addition, by predicting the sequential activation of neural genes, we were able to reconstruct several differentiation programs, similar to lineage trees, showing us how the progenitors progress to one cell type or another after their last division.”
The researchers also conducted a second analysis. If the right eye mainly connects essentially to the left side of the brain, and vice versa, a small fraction of neurons in the right eye make connections in the right side of the brain. Indeed, all species with two eyes with overlapping visual fields, such as mammals, must be able to mix information from both eyes in the same part of the brain. This convergence makes it possible to see binocularly and perceive depths or distances. “Knowing this phenomenon, we have genetically and individually “tagged” the cells in order to follow each of them as they progress to their final place in the visual system,” says Quentin Lo Giudice. By comparing the genetic diversity of these two neural populations, researchers discovered 24 genes that could play a key role in three-dimensional vision. “The identification of these gene expression patterns may represent a new molecular code orchestrating retinal wiring to the brain,” adds Dr. Fabre.
Towards regenerative medicine
Even before the neurons reach the brain, they must leave the retina through the optic nerve. The last part of this study identified the molecules that guide neurons on the right path. Moreover, these same molecules also allow the initial growth of axons, the part of neurons that transmits electrical signals to the synapses and thus ensures the passage of information from one neuron to another, as well as about twenty genes that control this process. This discovery is a fundamental step forward for regenerative medicine.
The more we know about the molecules needed to appropriately guide axons, the more likely we are to develop a therapy to treat nerves trauma. “If the optic nerve is cut or damaged, for example by glaucoma, we could imagine reactivating those genes that are usually only active during the embryonic development phase. By stimulating axon growth, we could allow neurons to stay connected and survive,” explains Dr. Fabre, who plans to launch a research project on this theme. Although the regeneration capacities of neurons are very low, they do exist and techniques to encourage their development must be found. Genetic stimulation of the damaged spinal cord after an accident is based on the same idea and is beginning to show its first successes.
The Kodjabachian lab at the Institute of Developmental Biology of Marseille (IBDM) is seeking a talented postdoctoral scientist with strong background in Cell and/or Developmental Biology, and a keen interest in integrative quantitative biology and interdisciplinary research. Our lab uses advanced imaging techniques (such as confocal videomicroscopy, super-resolution microscopy and 3D electron microscopy) to study the biology of ciliated epithelia at multiple scales.
In vertebrate ciliated epithelia, flows of biological fluids are powered by the coordinated beating of myriads of cilia harbored by multiciliated cells (MCC). This highly choreographed phenomenon raises many biological as well as physical questions among which, MCC spatial organization and at a lower scale centriole multiplication and orientation, as cilia stand upon modified centrioles called basal bodies. The selected candidate will join efforts to decipher the molecular mechanisms underlying these processes, using Xenopus epidermis, inducible MCC culture, and mouse post-natal brain as models.
IBDM offers a vibrant, international, and interactive environment to study the fundamental principles of cell and developmental biology. Furthermore, collaboration with theoreticians, physicists and numerical simulators are being developed on campus, from which our team has started to benefit.
The ideal candidate must hold a PhD for less than two years, and have skills in cell culture, cell imaging, molecular biology, and biochemistry. The position is opened for 3 years starting in December 2019. Applicants must email a CV, a statement of interest and contact details for 2-3 references to laurent.kodjabachian@univ-amu.fr. Applications will be reviewed as received, so motivated applicants are encouraged to apply as soon as possible.
Relevant publications:
Boutin and Kodjabachian. 2019. Current Opinion in Genetics and Development
Our research investigates the fundamental question of how cardiac cells sense and respond to their environment. We seek to understand the mechanisms underlying the regulation of morphogenetic and identity transformations that occur during development and disease. We use the assembly of the heart tube in zebrafish as our model with which to elucidate these mechanisms. Some of the specific research questions we are interested in include: How do multiple tissues interact to regulate large movements and biomechanical force? How do dynamic changes in the extracellular matrix regulate cardiac morphogenesis? How is lumen formation intrinsically and extrinsically encoded? and How is the plasticity of cardiovascular identity regulated? To answer these questions, we take an interdisciplinary approach, combining the genetic and live-imaging strengths of zebrafish with both biomechanics and systems-level methodologies.
If you are interested in joining our lab as a PhD student, please contact us directly at josh@olemiss.edu.
-Additional positions, including a rotation program, are also available in our interdisciplinary graduate program in the department of Biology at the University of Mississippi. For more information about our graduate program including rotations please see biology.olemiss.edu
We seek a biocurator to join the FlyBase group at the University of Cambridge, UK. If you are looking for a fulfilling, fly-related career away from the lab, and enjoy the challenge of organizing complex data clearly and concisely, then this is the job for you!
FlyBase curators extract biological information from scientific articles about the model organism Drosophila melanogaster, recording and organizing these data in template forms and graphical interfaces. Phenotype curators focus on data that illuminate the function of genes based on their mutant phenotypes and genetic interactions. All curated data are subsequently integrated into our central database and made freely available via the FlyBase website.
Additional responsibilities of phenotype curators include: developing strategies/tools to improve curation; enhancing data display/querying on the website; and interacting with the research community through HelpMail and presentations/help desks at research conferences. Curators also contribute to FlyBase publications and have the opportunity to develop computational skills (e.g. Unix, scripting, SQL).
I am pleased to announce a new collaborative interest initiative called DevoWormML, based on work being done in the DevoWorm group. DevoWormML will meet on a weekly basis, and explore the application of machine learning and artificial intelligence to problems in developmental biology. These applications can be geared towards the analysis of imaging data, gaining a better understanding of thought experiments, or anything else relevant to the community.
While “ML” stands for machine learning, participation can include various types of intelligent systems approaches. Our goal is to stimulate interest in new techniques, discover new research domains, and establish new collaborations. Guests are welcome to attend, so if you know an interested colleague, feel free to direct them our way.
Meetings will be Wednesdays at 1pm UTC on Google Meet. Discussions will also take place on the #devowormml channel of OpenWorm Slack (request an invitation). We will discuss organizational details at our first meeting on September 4. If you cannot make this time but are still interested in participating, please contact me. Hope to see you there!
Deficiency in the endocytic adaptor protein PHETA1/2 impairs renal and craniofacial development
Kristin M. Ates, Tong Wang, Trevor Moreland, Rajalakshmi Veeranan-Karmegam, Priya Anand, Wolfgang Wenzel, Hyung-Goo Kim, Lynne A. Wolfe, Joshi Stephen, David R. Adams, Thomas Markello, Cynthia J. Tifft, William A. Gahl, Graydon B. Gonsalvez, May Christine Malicdan, Heather Flanagan-Steet, Y. Albert Pan
The enteric nervous system of the human and mouse colon at a single-cell resolution
Eugene Drokhlyansky, Christopher S. Smillie, Nicholas Van Wittenberghe, Maria Ericsson, Gabriel K. Griffin, Danielle Dionne, Michael S. Cuoco, Max N. Goder-Reiser, Tatyana Sharova, Andrew J. Aguirre, Genevieve M. Boland, Daniel Graham, Orit Rozenblatt-Rosen, Ramnik J. Xavier, Aviv Regev
The skin’s germinative layer from Joost, et al.’s preprint
A molecular cell atlas of the human lung from single cell RNA sequencing
Kyle J. Travaglini, Ahmad N. Nabhan, Lolita Penland, Rahul Sinha, Astrid Gillich, Rene V. Sit, Stephen Chang, Stephanie D. Conley, Yasuo Mori, Jun Seita, Gerald J. Berry, Joseph B. Shrager, Ross J. Metzger, Christin S. Kuo, Norma Neff, Irving L. Weissman, Stephen R. Quake, Mark A. Krasnow
Generation of human neural retina transcriptome atlas by single cell RNA sequencing
Samuel W. Lukowski, Camden Y. Lo, Alexei Sharov, Quan H. Nguyen, Lyujie Fang, Sandy S.C. Hung, Ling Zhu, Ting Zhang, Tu Nguyen, Anne Senabouth, Jafar S. Jabbari, Emily Welby, Jane C. Sowden, Hayley S. Waugh, Adrienne Mackey, Graeme Pollock, Trevor D. Lamb, Peng-Yuan Wang, Alex W. Hewitt, Mark Gillies, Joseph E. Powell, Raymond C.B. Wong
DUX4 regulates oocyte to embryo transition in human
Sanna Vuoristo, Christel Hydén-Granskog, Masahito Yoshihara, Lisa Gawriyski, Anastassius Damdimopoulos, Shruti Bhagat, Kosuke Hashimoto, Kaarel Krjutškov, Sini Ezer, Priit Paluoja, Karolina Lundin, Pauliina Paloviita, Gaëlle Recher, Vipin Ranga, Tomi Airenne, Mahlet Tamirat, Eeva-Mari Jouhilahti, Timo Otonkoski, Juha S. Tapanainen, Hideya Kawaji, Yasuhiro Murakawa, Thomas R. Bürglin, Markku Varjosalo, Mark S. Johnson, Timo Tuuri, Shintaro Katayama, Juha Kere
An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis
Guanjue Xiang, Cheryl A. Keller, Elisabeth Heuston, Belinda M. Giardine, Lin An, Alexander Q. Wixom, Amber Miller, April Cockburn, Jens Lichtenberg, Berthold Göttgens, Qunhua Li, David Bodine, Shaun Mahony, James Taylor, Gerd A. Blobel, Mitchell J. Weiss, Yong Cheng, Feng Yue, Jim Hughes, Douglas R. Higgs, Yu Zhang, Ross C. Hardison
Modeling and treating GRIN2A developmental and epileptic encephalopathy in mice
Ariadna Amador, Christopher D. Bostick, Heather Olson, Jurrian Peters, Chad R. Camp, Daniel Krizay, Wenjuan Chen, Wei Han, Weiting Tang, Ayla Kanber, Sukhan Kim, Jia Jie Teoh, Sabrina Petri, Hunki Paek, Ana Kim, Cathleen M. Lutz, Mu Yang, Scott J. Myers, Subhrajit Bhattacharya, Hongjie Yuan, David B. Goldstein, Annapurna Poduri, Michael J. Boland, Stephen F. Traynelis, Wayne N. Frankel
Autophagy mediates temporary reprogramming and dedifferentiation in plant somatic cells
Eleazar Rodriguez, Jonathan Chevalier, Jakob Olsen, Jeppe Ansbøl, Vaitsa Kapousidou, Zhangli Zuo, Steingrim Svenning, Christian Loefke, Stefanie Koemeda, Pedro Serrano Drozdowskyj, Jakub Jez, Gerhard Durnberger, Fabian Kuenzl, Michael Schutzbier, Karl Mechtler, Signe Lolle, Yasin Dagdas, Morten Petersen
Integrated Multi-omic Framework of the Plant Response to Jasmonic Acid
Mark Zander, Mathew G. Lewsey, Natalie M. Clark, Lingling Yin, Anna Bartlett, J. Paola Saldierna Guzmán, Elizabeth Hann, Amber E. Langford, Bruce Jow, Aaron Wise, Joseph R. Nery, Huaming Chen, Ziv Bar-Joseph, Justin W. Walley, Roberto Solano, Joseph R. Ecker
The importance of barrier-free use of colors in images and graphs has been highlighted in letters to editors (Miall, 2007), papers (Geissbuehler and Lasser, 2013, Levine, 2009), editorials (anonymous, 2007), columns (Wong, 2011) and on numerous web pages. One of the recommendations is to use a color blindness simulator. Having a color vision deficiency myself, I cannot judge whether these tools work well. Nevertheless, a trial-and-error based approach seems rather inefficient. Instead, the use of (a number of) default color blind friendly palettes would be much more straightforward. For instance, green and magenta colors are the default choice for the production of color blind friendly overlays of fluorescence images. Below, I discuss a number of color palettes that are suitable for coloring graphical elements in plots. I think that people with a color vision deficiency would benefit from the implementation of these palettes in software for data visualization.
Qualitative color schemes
A quantitative color scheme is used when numbers need to be represented by colors. This conversion is done with a Look-Up Table (LUT). For more information on (colorblind-friendly) LUTs see this blog and this paper. Here, I talk about qualitative color schemes, which use colors to label different categories. The number of distinct categories define the number of unique colors that are needed. Ideally, these color can be distinguished by everybody.
For up to four categories, it is rather straightforward to come up with a set of colors that are easy to distinguish. Still, it does make sense to choose the colors from a color blind friendly color scheme. When 5-8 colors are needed to uniquely label different categories, it is a considerable challenge to find a suitable color palette. Beyond 8, it is close to impossible to find colors that can be readily distinguished. In these cases, alternative labeling methods are recommended. Below, several color blind friendly qualitative color schemes are described and four of those are shown in figure 1.
Color blind friendly palettes
Masataka Okabe and Kei Ito have proposed a palette of 8 colors on their website Color Universal Design (CUD). This palette is a “Set of colors that is unambiguous both to colorblinds and non-colorblinds”. The use of this palette is supported by others (Wong, 2011; Levine, 2009) and it is the default scale for the book “Fundamentals of Data Visualization” by Claus Wilke.
Martin Krzywinski has a website with 12- and 15-color palettes that offer more choices. Personally, I have difficulty with distinguishing several of these colors. Also, it is recommended to use no more than 8 different colors. Therefore, these palettes will not be taken along.
Paul Tol has created several qualitative color schemes that are color blind friendly. These palettes have 5-10 colors (including grey) and vary in darkness.
Figure 1: An overview of qualitative, color blind friendly palettes. The figure was produced with an R-script that defines and plots the palettes (doi: 10.5281/zenodo.3381072).
Choosing a color scheme
Which of the palettes is the best? This is hard to say for several reasons. Colors look different when printed, shown on a screen, or projected with a beamer. Next to this, size, structure and position of the objects will determine whether the categories can be distinguished. As a consequence, it is probably impossible to come up with a single universal color palette. I think that the palette designed by Okabe&Ito is a good first choice. Still, it is a good idea to see how different palettes perform when they are used in realistic data visualizations. As an example, figure 2 shows four plots in which the different color blind friendly palettes are used to label 6 lines.
Figure 2: The color palettes shown in figure 1 are used to uniquely label 6 different lines in a realistic data visualization. The graphs are with made with PlotTwist.
The palettes shown in figure 1 are implemented in the webtool PlotTwist (Goedhart, 2019). PlotTwist is a freely available online tool for plotting and annotating time-series data. It enables anyone to experiment with the color blind friendly palettes and apply them to lineplots. I encourage you to share your opinion on these (or any other) palettes and how they perform (especially if you have a color vision deficiency). To do so, you may leave a reply below or share your thoughts on twitter. Ultimately, I hope to see more data visualizations that pass a color blindness test with flying colors.
Recommendations
I will end with some recommendations aimed at improving graphs that use color:
-Use a color blind friendly palette by default.
-Use thick lines or large symbols to make it easier to correctly identify and map the color to a legend.
-In addition to colors, consider the use of patterns or labels to distinguish between categories.