Researchers at the Big Data Institute and colleagues have developed a new method for understanding the relationships between different DNA sequences and where they come from.

This information has widespread applications, from understanding the development of viruses, such as SARS-CoV-2, the strain of coronavirus that causes COVID-19, to precision medicine, an approach to disease treatment and prevention that takes into account individual genetic information. The study is published in GENETICS and is the featured paper in the September 2024 edition.  

Genetics is rapidly becoming part of our everyday lives. Nearly every week sees another newspaper headline about genetics and human ancestry, with huge datasets of DNA sequences routinely generated and used for medical study.

We can make sense of this genomic big data by working out the historical process that created it ‒ in other words, where the DNA sequences came from. If we take a small section of someone’s DNA we know it must have come from one of their two parents in the last generation, and previously from one of their four grandparents in the generation before that, and so on. This means we can represent the history of different sections of DNA by tracing them backwards through time.

If we do this for a large set of DNA sequences from different people, we can build up a set of genetic “family trees,” a genealogy of DNA sequences. This grand network of inheritance is sometimes called an ancestral recombination graph (ARG). Previous work by the same research group has shown that such networks can be used not only to illuminate the history of our genome, but also to compress DNA data and speed up genetic analyses.

Lead author and evolutionary geneticist at the Big Data Institute, Dr Yan Wong said, “There has been surprisingly little consensus on exactly how to represent such an ancestral recombination graph on a computer. In this study, we outline a simple and efficient encoding of genetic genealogies in which each ancestor can be thought of as a fragmentary length of DNA, or ‘ancestral genome’ at some point in the past. The history of today’s genetic sequences is traced back through those ancestral genomes, keeping track of which chunks of DNA were inherited from which ancestors.”

By using this simple scheme, recording genome-to-genome transmission of information, the study shows that the same genetic ancestry can be stored to different degrees of precision. This means relationships between different DNA sequences can be represented without having to know or guess the precise timing of joins and splits that underlie the true history of inheritance. The researchers also show that their description of genetic inheritance is flexible enough to deal with the wide variety of different methods that researchers currently use to reconstruct genetic history.

The approach allows scientists to store and analyze large amounts of genetic data on a standard laptop, and it generalizes to any species of life on earth. For example, it forms the basis of a “unified genealogy” of over 7,000 publicly available whole human genome sequences that the researchers released previously. They are currently creating a genetic genealogy of millions of SARS-CoV-2 genomes, collected over the span of the coronavirus pandemic, which will allow analysis of the recent history of the virus, pinpointing the emergence of novel mixed (or “recombinant”) strains. Dr Wong added, “We hope that this formal standard for how to represent genetic genealogies can help to unify the field of genetic history and make it easier for scientists to analyze, share and compare results. This will be crucial as we move into an era of genomic medicine, where genetic data will be used to diagnose and treat diseases, and where understanding the history of our genomes will be key to understanding our health and ancestry.”

A new associate editor is joining GENETICS in the Theoretical Population and Evolutionary Genetics section. We’re excited to welcome Sarah Otto to the editorial team.

Sarah Otto
Associate Editor

Sarah (Sally) Otto is a Killam University Professor at the University of British Columbia. Her research focuses on modelling how inheritance and reproductive systems evolve by investigating the selective forces acting on genetic systems (recombination, ploidy level, gene duplications) and mating strategies (sexual vs asexual reproduction, sexual selection, floral reproductive strategies).  Complementing this approach, Otto’s group tracks yeast as they evolve to test evolutionary theories. Recent work, both theoretical and experimental, has focused on evolutionary dynamics in a rapidly changing world. During the pandemic, she worked to clarify the impact of evolutionary changes on the SARS-CoV-2 virus and public health implications. With over 200 publications and a book, her awards include a MacArthur Fellowship, a Steacie Fellowship and Steacie Prize, and fellowships in the Royal Society of Canada, the American Academy of Arts and Sciences, and the National Academy of Sciences. 

We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates.

Sarah Petrosky
Multimedia Subcommittee
University of Pittsburgh

Research Interest

I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation are changing. This process seems to be more dynamic than we had expected. Many traits are governed by more than one gene, or are polygenic, so when going from one phenotype to another, changes might need to occur in multiple genes. It is easy to think of this process as linear, where all individuals with the same phenotype have the same variation at the genetic level. It is possible, however, that this process is more patchwork, where multiple individuals may have the same appearance yet are genetically different, or heterogeneous. My doctoral work thus far has been dedicated to dissecting a polygenic, heterogeneous trait in African populations of the fruit fly Drosophila melanogaster.

As a PhD-trained scientist, you have many career options. What interests you the most?

I am passionate about science communication and would love a career that involves sharing current research with the general public. It is my responsibility to help the people in my life understand the impacts of the natural world on their daily lives. I have dedicated a lot of time to the way I present my work so that others can understand my perspective. Previously, I have been involved with a transdisciplinary research group that included biologists, literary scholars, artists, and historians, among others. I recognized quickly that, in meetings with this group, I could not speak about my portion of the research project in the same terms as I would with other biologists, so I took classes in rhetoric and literature to improve my communication skills with those outside my field. Helping my colleagues understand work that is outside of their wheelhouse was rewarding, and in turn, they shared their expertise. This type of relationship, where we are consistently teaching and learning from each other, is valuable, and I would like to continue having this discourse in my career. I enjoy breaking down my work into easily digestible terms, in both the written word and the spoken word. For my future career, I would enjoy writing for the science sections of large publications or working as a communications liaison to foster more effective discourse between scientists and nonscientists.

In addition to your research, how do you want to advance the scientific enterprise?

It is important that my work be accessible to people at varied stages in their development as scientists and that I can break down concepts for non-scientists. Science can intimidate those with little training, so I want to be able to present my work in a way that is not intimidating but welcoming. Creativity is vital to the scientific process, and I want to present an image of science as a creative process that anyone can pursue. When we encourage creative thinking in research, we can make connections that we otherwise might have missed. My own work benefits from being open-minded to the unexpected, and my creativity and willingness to think outside the box have reinforced my research.

In addition, interdisciplinary collaboration has greatly strengthened my past research, and continues to strengthen my current thesis work. When people with varied perspectives work together on a problem, they can sometimes reach a deeper, more satisfying understanding. As an evolutionary developmental biologist, I currently collaborate with a population geneticist. Evolutionary developmental biology and population genetics are two fields that have notoriously different viewpoints on evolution. I have had to work to reconcile these differing views, and I believe both my project and I have improved due to this collaborative relationship. I aim to use my previous experiences to encourage and promote unexpected collaborations.

As a leader within the Genetics Society of America, what do you hope to accomplish?

As a member of the Multimedia Subcommittee, I am involved in developing the ECLP’s podcast, Genetics in Your World. All my contributions to the podcast are done with broad accessibility in mind. I hope that the podcast episodes I have contributed to will be enjoyable not just for geneticists, but students just embarking on their scientific journey. I aim to produce content that is not only informative to scientists at all stages of their career but also relatable and enjoyable. I want scientists who are interested in being on the podcast to feel comfortable telling their stories, and I encourage genuine communication. In addition, I hope that my nonscientist family and friends can listen to my contributions to the podcast and follow along with the conversations.

Previous leadership experience

I have mentored multiple rotation students and undergraduate researchers. I was involved with the University of Pittsburgh’s Gene Team to help the students prepare for college applications. I have taught and given multiple guest lectures, including one at the Community College of Beaver County (CCBC). CCBC lost its wet labs during the COVID-19 pandemic, so I organized a day in the lab for the students. There, members of the lab and I guided them through some of the techniques we use in the lab to give them exposure to an authentic research environment. I was heavily involved in developing a museum exhibit that is still in rotation at the Virginia Museum of Natural History in Martinsville, VA. I was also a founding member of the Dragon Research Collaborative at Roanoke College during my undergraduate education.

In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the GSA Early Career Scientist Policy and Advocacy Subcommittee.

Today, as part of the ECLP Policy and Advocacy Interview Series, I’m with Maria Elena Bottazzi, current Senior Associate Dean of the National School of Tropical Medicine at Baylor College of Medicine.

Could you tell us a little bit more about your career path and your current work at Baylor?

I am an Italian-born, Honduran-raised microbiologist. I received a microbiology and clinical chemistry degree from the National Autonomous University of Honduras. In Honduras, as is the case with most Latin American countries and other low-middle income settings, training at the bachelor’s-in-science level rarely involves experience within molecular biology. So, in order to further understand the molecular and biochemical basis of host-pathogen interactions, I moved to the United States to complete my PhD at the University of Florida, [studying the] molecular basis of pathogenic disease. As I was completing my postdoctoral work at University of Pennsylvania, I realized that my true calling was using all I have learned in the biomedical field to create solutions and develop new interventions for tropical and emerging diseases. So, I decided to enroll in a Master of Business Administration program to hone my business management and organizational skills. Shortly after, I met Peter Hotez (the current Dean of the National School of Tropical Medicine) and realized we were both interested in the same goal: developing global health technologies and translating them from the academic laboratory to the world. We have since worked together with an emphasis on vaccine development and accessibility for developing countries and for diseases that are typically ignored.

You have worked with vaccines and neglected tropical diseases for a while. What has been your own level of involvement in the policy area around these issues? Do you have any advice for young scientists interested in science policy?   

I have been around tropical diseases my whole life. Growing up in Honduras and studying microbiology there, I have always been observing the devastating effects they have on people. But to be fair, my interest peaked around the time I was finishing my higher education. This coincided with the turn of the century, when there was a re-emerging interest in global and tropical health. As I started my professional career, I saw all these policy frameworks being developed around poverty, hunger, education, and other health factors. Yet, as I moved forward with my scientific path, we started seeing how several diseases were being ignored, especially those that affected only tropical countries. I found myself part of a drive towards open science and creating partnerships and collaborations that would make research in tropical diseases accessible and transparent. Very early on, Peter Hotez and I realized that we needed to go beyond the bench: we had to be capable of developing robust products, like vaccines, that would be able to directly help people. Besides our scientific language, we also had to learn policy, business, ethics, and legal languages to serve the community in the best way possible. As scientists, it is difficult to be properly trained on these other dimensions: you are usually focused on the science and presentation skills. Peter Hotez was a great role model for me. He was really interested in the behind-the-scenes of policy making, so I ended up tagging along for the ride. Eventually, I realized I was very interested in scientific policy, so I applied to and got selected for a fellowship with the Leshner Leadership Institute in the American Association for the Advancement of Science. There I got formal training on how to integrate academic sciences and business practices. It is not all about the formal training, however. During my personal time, I also took several courses and met with different people to learn more about pharmaceutical economics, licensing and intellectual property laws, and even how to write legal contracts. This is something I recommend to every early career scientist: make sure that you take advantage of all the resources out there. Branch out from your bench, and learn about things that will help you engage the community and your own science in a much more efficient way! In the real world, you are always surrounded by so many more things than just your science. Always try a holistic approach when it comes to preparing your own career path.

You and Peter Hotez developed a COVID vaccine. Can you tell us more about it and how any regulations impacted your work?

As Peter and I started working on neglected tropical disease vaccine programs, we realized a pattern: funding for these programs dramatically increases when the disease emerges, but then it rapidly decreases as other priorities arise. We decided to take advantage of all the knowledge created during the “golden years” of funding for these rare diseases, and in 2011, we were awarded a grant to tackle a Severe Acute Respiratory Syndrome (SARS) vaccine in case of future outbreaks. Between 2011–2014, we were incredibly successful: we developed and manufactured a candidate for a SARS vaccine and were close to moving into human trials. Then, the 2015 Middle Eastern Respiratory Syndrome (MERS) outbreak happened; the NIH asked us to use the rest of the funding to develop a MERS vaccine instead of moving the SARS vaccine into toxicology trials. By the end of 2016, we had already come up with a prototype vaccine for SARS and for MERS as well; we were ready to start a pathway towards the clinic for these vaccines. Then, suddenly, coronaviruses were not that important anymore; our direct funding for these vaccines stopped as the agencies believed they had other diseases to deal with at that point. Internally, we decided to keep the program alive with some intramural money so all the scientific knowledge wouldn’t be wasted.  

To our surprise, the 2020 pandemic was being caused by a coronavirus family virus with a sequence similar to the SARS virus: we were ready to hit the ground running! Instead of 4 years, it only took us a few months to figure out the COVID-19 prototype vaccine. Since the world was in a state of urgency, we decided to not patent our COVID-19 vaccine technology and offered it as open source for manufacturing to different companies. Sadly, no company in the US or Europe was interested. This was mainly due to both scientific and policy misunderstandings. Our vaccine was based on the spike protein’s receptor binding domain and was produced in yeast, so it was easily scalable. At the time, both pharmaceutical companies and policy makers worked under the false assumption that the whole spike protein must be used, and they would rather fund new technologies such as mRNA-based vaccines because of their perceived speed to develop although they were not nearly as scalable at that time. Although we had pre-clinical trial data proving the high efficiency of our vaccine prototype, big pharmaceutical companies had no interest in it due to both policy and scientific mishaps. Eventually, we received interest from companies in India and Indonesia since they were having a hard time getting access to the mRNA vaccine technologies. These manufacturers shared our same vision to make scalable, affordable, and equitable vaccines for the public. We now have administered more than 100 million doses, making our vaccine one of the most accessible ones out there. Thankfully, we were able to surpass initial hurdles and make the vaccine accessible to those who needed it the most.

As a vaccine expert, do you think we are prepared for the next pandemic? What do you think needs to change regarding current vaccine policies?

One of the main issues during this pandemic was how countries with lots of resources decided to over-stock vaccine doses and disregard the needs of other countries. Nationalism plays a big part in this; everyone wants what is best for their own people first. Yet, as we clearly saw with the failed response to this pandemic, this is not the correct way to go about public health. Even if you vaccinate all your citizens, you will still suffer the downsides of a pandemic if your neighbors and trade partners cannot do the same. We learned the hard way that to get completely out of a pandemic, we need the whole world to work together and help each other.  

I think we learned a lot during this pandemic that will be useful in the future. For example, regulators around the world realized that many steps of the process could be done in parallel instead of sequentially, so we now know that the pipeline to create and manufacture vaccines, or other drugs, can be shorter and more efficient. Yet, we still face a terrible monster: inequality. With high-income countries overstocking vaccine doses, many low-income countries were left without the opportunity to order vaccines. Even after some countries started donating doses for children and senior adults, many low-income countries had their whole health system collapse due to how long it took to access vaccines. In the long run, this deeply affected high-income countries since the world was not able to truly go “back to normal” until most countries had regained control over their health systems. By not making vaccines equitable, we kind of shot ourselves in the foot and prolonged the pandemic far beyond what it could have been if we had made vaccines readily accessible to everyone since the beginning. We learned some lessons from this pandemic; however, we still have much work to do if we want to be prepared for another one. It is not only vaccine accessibility that needs to be more equitable but also vaccine research and regulation. There is a common belief that anything that is manufactured in middle- or low-income countries is, by default, of poor or dubious quality. If we want to be ready, we need to trash that old mentality. Worldwide regulators, like the World Health Organization, should work harder to improve vaccine research, manufacturing, and regulatory enterprises in low-income countries. With COVID, we clearly saw how economic power bought you a ticket to the discussion table. We need to move forward and show that you do not need economic power to have a voice regarding the world’s public health.

Thanks for being with us today. Do you have any final words for prospective scientists in developing countries who think their dream of being a researcher is far-fetched?

No dream is too far-fetched. I would like to tell them that, although it can be hard, they need to leave the impostor syndrome behind. It does not matter if you graduate from your country’s national university or from Harvard. You don’t need a prestigious degree to do great science. You need dedication, passion, courage, and consistency. You have been exposed to very different life stories than the average scientist. You need to take advantage of that cultural intelligence and let it propel you to success. I believe those of us who come from low-income countries are well suited for science; we are accustomed to surviving crisis after crisis, and our resilience is beyond that of anyone else. Our culture, our language, and all our lived experiences are strengths that prepare us for a bright future. Be proud of who you are and where you come from and leverage that to increase your skills. Do a self-evaluation, identify your weak spots, and use all that resilience to move forward. You have all the potential to become successful scientists. Never stop working hard and aiming for the top!

Guest post by A.J. Marian Walhout, PhD.

Massachusetts, March 2020: The early days of the COVID-19 pandemic that would profoundly affect us all. Labs shut down abruptly, assay trials were disrupted, some experiments in progress were thrown out. Now what? With pipettes unused on the bench and the foreseeable future unclear, how long would this take? A week or two? Oh, how naïve we were. Many labs pivoted to do research on the new virus, leading to many papers, demonstrating that publishing doesn’t have to take months. But I digress… When the lockdown started, I immediately thought my lab could use this time to work on a project that I always wanted to start but never seemed to have the time for. I discussed this project with the lab via the relatively new Zoom platform we are all so familiar with now. (Anybody know how they outcompeted Skype?)

In my lab in the Program in Systems Biology at the University of Massachusetts Medical School, we study how metabolism affects gene expression and vice versa. We do this at a network level using the nematode Caenorhabditis elegans as a model system. Over the years, we and others had made great strides in gaining insights into transcriptional networks. More recently, we had reconstructed a genome-scale metabolic network model, which we can integrate with gene expression data to understand how the two biological processes affect each other. 

However, in many studies, we found that relatively straightforward online visualizations of C. elegans metabolic pathways were lacking, and we were drawing pathways by hand on scraps of paper or on white boards to help us understand our results and to derive novel hypotheses. Popular (and excellent) tools such as KEGG provide visualizations, but we found these “pan-organism” maps to be often incomplete and cumbersome to navigate due to gaps in the pathway, missing genes, or genes assigned to incorrect pathways. My dream was to have a map for metabolism similar to traffic maps on mobile devices where one could “travel” from one metabolite to another via different routes and be able to zoom in and out to see which enzymes and transporters are involved in which reactions. This is, of course, very hard to do. So, at the start of the lockdown/work-from-home phase of the pandemic, we embarked on a group project to draw maps for individual C. elegans metabolic pathways using a standardized format and make these available on our WormFlux website . We first agreed on where a pathway starts and ends, which is not a trivial task because pathways all connect into the larger metabolic network. We settled on a total of 62 pathways and assigned each pathway to a duo or trio of lab members, making sure they would work with different colleagues on different pathways via video conferences. This approach ensured that lab members talked to each other, worked together, and communicated with the larger group, which helped to keep a sense of purpose and morale during this very strange time. 

Lab members drew maps in different ways; there was a lot of freedom and creativity in map making. An example can be seen in the image to the right. When we agreed that the pathway was complete and correct, a team generated the pathway in a standardized format that could be uploaded to the internet. Another team would then double-check the pathway before it was uploaded to WormPaths, which is part of the WormFlux website. A standardized drawing for WormPaths is shown in the image. Standardization took much more time and extended long after the lockdown ended, but by then we were all committed to seeing the project through. In WormPaths, pathways are not only visualized and connected to each other, they are also searchable, printable, and downloadable in three formats. Moreover, we generated a tool for pathway enrichment analysis, for instance of gene expression data. A manuscript describing this project in detail is online in GENETICS.

WormPaths has become an essential part of our daily research. It is one of our projects and papers that fills me the most with joy; I am exquisitely proud of how my lab worked together during one of our most trying times. We expect WormPaths to be of great use to the C. elegans community and welcome any corrections or feedback on the maps. Now, all we have to do is create that metabolism navigation app, so we can search the network on our mobile phones! 

About the Author:

Dr. A.J. Marian Walhout, PhD, is the Maroun Semaan Chair in Biomedical Research, Co-Director of the Program in Systems Biology, and Professor in the Program in Molecular Medicine. Dr. Walhout is a pioneer in Systems Biology. Her group has gained numerous insights into how genes function in the context of complex biological networks that connect regulatory processes and metabolism. She has gained insights into how vitamins in our diet affect gene regulatory and metabolic networks that control development, growth and overall health. Her findings offer opportunities for personalized medicine to prevent and treat a variety of both rare and common human diseases.

Quick tips for making vaccine science understandable to non-scientists.

Guest post by Elisabeth Marnik, Ph.D.

It’s been more than a year since the world started shutting down in the wake of widespread COVID-19 cases. We are still living through a pandemic, but the United States is finally starting to see a light at the end of the tunnel thanks to the emergency use approval of three COVID-19 vaccines. 

However, distrust in science and skepticism about the vaccines’ safety continue to pose a risk to herd immunity. As a scientist and a science communicator, I feel strongly that we need to be sources of sound and understandable scientific information, which led me to launch a science social media presence. In the process, I’ve learned a lot about how to make the science around vaccines understandable to non-scientists. Here are some tips I’ve learned to help make your conversations and interactions more productive. 

Focus on specific concerns and make the information understandable.

When deciding what to address, start with the common concerns you hear many people expressing and break them down one by one. These usually relate to safety, effectiveness, ingredients, and the unprecedented speed with which the vaccines were developed. You can also ask the people in your life what they’re worried about. Focus the information you share on those main topics and break them down into small segments. Then weave those pieces into conversations, social media posts, or other avenues. This prevents people from getting overwhelmed by a lot of new information all at once. 

Much of the vaccine information is complicated and confusing, so it’s very important to be careful in choosing the words you use to address these concerns. Avoid jargon. If it’s necessary, be sure to define it. Use stories and images to illustrate the points. The key here is to remember you’re talking to people without formal scientific training. It’s best to simplify and then add more information as they ask questions.

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Remind people why the vaccines are safe. 

As mentioned above, one of the biggest concerns pertains to vaccine safety. Many worry that scientists skipped safety steps in order to make these vaccines so quickly. However, we know that is not true. Scientists were able to pivot and use the foundation of work done on SARS, MERS, and RNA therapies to produce these COVID-19 vaccines in record time. All phases of the trials still occurred but overlapped to save time. Many people do not realize this. 

It can also be helpful to contextualize the risks of getting vaccinated. Anything we do, including receiving a vaccine, has potential risks. However, the risks of vaccines are very low compared to the risks of many other things we do everyday, like driving or taking birth control pills. The risk is also much lower than the risk from COVID-19 itself. There being small risks does not make something unsafe. 

Emphasize why getting vaccinated is important. 

There are a few things to focus on when explaining why people should get vaccinated.

The first one is that it reduces the chances of infection and bad outcomes, such as hospitalization and death. That is important for decreasing the risk of COVID-19 and ensures that vaccinated people have the best chance for survival if they do contract the virus.

There is also increasing evidence that the vaccines reduce the likelihood of transmission and asymptomatic disease. Both of these things will help us protect others and help reduce overall cases. 

The final point is that we know that long COVID—now called post SARS-CoV-2 sequela—is a risk. It is a risk even in those with mild infection who are young and otherwise healthy. The impact of long COVID has been widely reported. I also put together a long COVID series on my science Instagram account. Getting vaccinated decreases a person’s risk of infection, so it also decreases their chances of developing long COVID. There are also some emerging hypotheses that vaccines help improve long COVID symptoms in those who have already been infected, but more data is needed. 

All of these things will combine to result in less overall infections and less burden of disease in those who do get infected after vaccination. This makes vaccines worthwhile, and it offers a strong argument against vaccine resistance. However, don’t forget to remind people that wearing a mask in public will still be important until more of the population is vaccinated!

Encourage people to get the first vaccine offered.

It’s very easy to get caught up in comparing the numbers for efficacy between the different vaccine types. It can be helpful to remind people that the vaccine trials were run at different times and in different places. Each trial also had a different way of defining symptomatic cases, so you can’t fairly compare their overall efficacy numbers to each other. The important thing is to stress that all three of the vaccines currently approved have been shown to be safe, protective against death, and effective at reducing your chances of getting infected. Also remind them that if they pass up a chance to receive a vaccine there is no guaranteeing when they’ll be offered the one they prefer. In the meantime, they will be fully vulnerable to a COVID-19 infection. Any vaccine is better than no vaccine, and while there may eventually be a time where people can choose, right now is not that time. 

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Discussing these issues with people who distrust science and vaccines

Conversations around COVID-19 and vaccines can be very difficult sometimes. However, having these conversations with people you know can help reassure them and change their mind if they’re hesitant. The most important thing is to understand what is driving their concern. Are they part of a marginalized group who have been mistreated by the medical community? Did they hear that a friend had a bad vaccine reaction? Are they worried because they don’t understand how research or vaccines work? Most of the distrust and hesitancy is due to fear, misinformation, or bad past experiences. Some of these fears are based in truth, others are not. It’s critical to listen to the motivating emotion and then address it with compassion. Do not minimize their concern. Their emotions are valid, whether or not the scientific facts behind them are.

Most people just want to keep themselves and their family safe. There is a lot of scary information that is untrue but easily accessible. It is understandable that people are worried. It is our job, as scientists, to be able to address these fears in a way that is not dismissive or confusing. 

Once you understand the person’s concerns, you can present information to address them. But do this in a way that is compassionate and addresses the emotion behind their concern. Find areas of common ground and build from there. Most of these conversations take time and considerable effort, so know when you need a break and exit the conversation. You can always pick up at another time.

About the Author

Elisabeth Marnik is an Assistant Professor at Husson University. Marnik is a member of the GSA’s Conference Childcare Committee and a past member and current advisor of the GSA Early Career Leadership Program’s Communication and Outreach Subcommittee.

As COVID-19 has spread across the world, members of the GSA community have faced unprecedented challenges in their professional and personal lives. To stay connected during this socially distant time, GSA invites the scientists in our community to share how they are meeting these challenges, as well as their questions and worries. 

If you would like to contribute to this series, please contact Communications Assistant Jacqueline Treboschi.

Guest post by Pinky Kain, PhD 

COVID-19 has been an unprecedented challenge that is keeping all of us on our toes, especially here in India. It sometime feels as if we are currently living in a science-fiction horror movie. The gruesome briefings by various scientists around the world and people who have experienced the illness are enough to give anyone goosebumps.

Being high-spirited is not easy when everyone is facing a huge health crisis with many unknown outcomes. We never thought the pandemic could actually last so long, challenging us in unusual ways. The more we learn about the virus and the harm it can do to us, the more anxious we feel. But the trick is not letting this tiny virus win. Such adversity is good at teaching us what we shouldn’t be doing in the future if we are trapped again.

My family, including my son, my husband, and I, left Delhi-NCR (Faridabad) on March 21, in the early morning, to meet my father-in-law. I was looking for a much –needed break, after organizing and finishing my week-long hectic workshop on Neurobiology at the Regional Centre for Biotechnology, in Faridabad, India (my current institute). I am lucky that I had organized this workshop on time, a task which seems impossible now.

I have been a Delhiite all my life, and I had never seen Delhi like this before. There was a deep silence, and hardly anyone on the roads. It took us only 3 hours to cover 155 miles and cross three different states. Finally, we arrived at Roorkee—my husband’s home city. We initially came to Roorkee just for a week, bringing only a handful of clothes, and absolutely nothing else. Since we remained here much longer than expected, we managed with whatever we had. My son sometimes even wore my short sleeve T-shirts to beat the heat during the day time. But honestly, we enjoyed our stay. With a lower pollution level during the lockdown and a couple of heavy rains, we were able to clearly see mountain ranges further north from our terrace for the first time.

A drawing by the author’s son

During quarantine, I learned so much from my five-year-old son. He was never worrying or feeling anxious. He was (and still is) happy studying online, learning new lessons, talking to his friends during the classes, getting enough time to play, and trying something new every day. He was busy with his space lessons, music, building blocks, e-books, and with his vast collection of cars (which he always carries with him). The best part of lockdown for him was that mummy was home full-time and could spend quality time with him. He has always hated the fact that I come home late and am never home when he comes back from school. We get a full Saturday and Sunday every week to spend with each other, and I avoid any lab work at that time in an effort to balance work and personal life. It is amazing to see how resilient kids are.

The lockdown was extended many times with new regulations, and we were not sure if we will be able to go back home since the state borders were sealed. Luckily, we had our laptops and data drives with us to work from home. Honestly, I was never being so busy before. Between cooking (my stress buster) and household chores, sitting with my son for his online classes, managing my lab from afar, writing, and making oil paintings, it was like there is no time to even breathe in between. Life has never been so versatile and challenging, yet organized. After many years of packed schedules, we were all at home for evening tea and snacks, to laugh together and discuss political and scientific issues at length. Sometimes my anxiety levels were high, when I was thinking of the new normal post-lockdown, and the challenges I will face in managing my lab. One of my students was stuck at the institute and staying in a hostel. He couldn’t leave for home on time before lockdown. I was making sure to talk to him every day.

Because of my experiences these past couple of months, I’ve realized we need to try not to think much about how long we will have to face this crisis. Instead, reinvent yourself, exercise, and get involved in stuff that you always want to do without worrying so much. The whole focus should be remaining happy and optimistic. Avoid any clashes with family members when anxiety levels are high. Try to enjoy family time, appreciate the sunrise and sunset, find music in silence, and enjoy fresh air. We all are on a ride on this bumpy road. Remember: nothing in nature blooms all year, so be patient with yourself. Now we are back to labs with people working in shifts and happily adjusting to the new normal with masks and sanitizers.

About the Author

Pinky Kain, PhD, is a Principal Investigator and Group Leader who works in the NCR Biotech Science Cluster, in Haryana, India. She is also a Wellcome Trust DBT Intermediate Fellow.

Guest post by Jennifer Tsang.

Years ago, Sarah Edie and Norann Zaghloul pored over 50,000 zebrafish embryos, examining them for developmental phenotypes. They had previously injected each of these embryos with a plasmid expressing a gene from chromosome 21. Their goal was to understand how overexpression of specific genes on chromosome 21 affected early development¹.

Little did they know that their research would become an important resource for COVID-19 research.

Sharing plasmids to the research community

At the time, Edie was a member of Roger Reeves’s lab at Johns Hopkins University School of Medicine where he studied Down Syndrome, and Zaghloul was a postdoc in Nicholas Katsanis’s lab. The team created a library of 164 plasmids—each expressing a different gene from chromosome 21—for the study, and they published their work in the Genetics Society of America’s journal, G3: Genes|Genomes|Genetics. 

“We knew from the time we decided to do the experiment that making this available to the larger research community would be one of the goals of the experiment,” says Reeves. The lab deposited each plasmid with Addgene, the nonprofit plasmid repository that would then distribute the plasmids to researchers.

“We thought primarily people who were involved in Down Syndrome research would be interested in these [plasmids],” says Reeves. Addgene sends a monthly report to depositing labs summarizing the requests they get for their plasmids. “It’s been very interesting to get the monthly report and see the people who are asking for these,” says Reeves. Requests have come from researchers around the world, some work in Down Syndrome and some do not.

From developmental studies to COVID-19

When the COVID-19 pandemic hit, Reeves began to survey genes on chromosome 21. Along with other members of the Trisomy 21 Research Society, he was interested to see if there were ways in which people who have trisomy 21 might be more susceptible or more resistant to the effects of the virus. The first coronavirus paper he read about the biology of SARS-CoV-2 mentioned TMPRSS2. “I said, ‘Wait a minute, that’s on chromosome 21,’” Reeves recalls. TMPRSS2 also happened to be one of the genes Edie and Zaghloul expressed in zebrafish and deposited at Addgene.

During SARS-CoV-2 infection, TMPRSS2 cleaves the SARS-CoV-2 spike protein which is required for viral and cellular membrane fusion. Without cleavage by TMPRSS2, the SARS-CoV-2 virus cannot enter host cells. As research labs shifted to COVID-19 research, Addgene began receiving requests for the TMPRSS2 plasmid. With 175 requests since the beginning of the pandemic, it has become one of the most asked for plasmid for COVID-19 research.

This plasmid is a great example of how two seemingly disparate fields share reagents and how open science allows for a broad reach. Another plasmid generated from the zebrafish study was also used in acute myeloid leukemia research. While researchers looking for these reagents are from different fields than the original study, they were able to find these resources through a centralized source.

This isn’t the only time that reagent sharing through a centralized repository has accelerated the speed of research during the COVID-19 pandemic. A mouse strain containing the hACE2 receptor that allows it to be infected with human SARS-CoV was deposited at Jackson Laboratory in 2007, meaning that scientists could easily get the mice for COVID-19 research. 

At Addgene, things are no different. Plasmids deposited from research into the 2003 SARS outbreak were already in the repository at the start of the COVID-19 pandemic. CRISPR plasmids deposited in the last few years have also become an important resource for developing CRISPR-based assays for detecting SARS-CoV-2 RNA and nucleic acids from other pathogens. The future of shared materials stored in repositories may be unpredictable at the time of depositing, but these materials have many possibilities.

1. G3: GENES, GENOMES, GENETICS July 1, 2018 vol. 8 no. 7 2215-2223

Written by members of the GSA Early Career Scientist Communication and Outreach Subcommittee: Angel F. Cisneros Caballero, Université Laval; Adelita Mendoza, PhD, Washington University; Narjes Alfuraiji, University of Manchester; Anna Bajur, Max Planck Institute of Molecular Cell Biology and Genetics

During the current global pandemic, public attention is increasingly falling on the process of drug discovery and development. How exactly do we find new treatments? And what does it take to bring them to the clinic? One powerful tool in this process that often escapes notice is bioinformatics—the use of computational resources to answer biological questions.

Exponential increases in computational power have revolutionized the way we do science. Over time, this has created entirely new fields of research, since we can now analyze more data efficiently and explore more complex algorithms and models¹. Bioinformatics is one of the fields made possible by this technological achievement, and it has been critical for many recent scientific advances². 

Bioinformatics comprises two interdisciplinary sub-fields that interface with computer science, mathematics, and biology: One is the research and development that scientists need to build the models modern biology requires. The other is computational biology, which is dedicated to understanding basic biological queries.

Bioinformatics is not just an academic field; it has many clinical applications. For example, we now have the technology to sequence genomes and identify genes involved in diseases, such as cancers. However, we can only do it accurately by looking at short segments at a time. Sequencing an organism’s genome becomes like a giant puzzle with thousands of pieces, and only bioinformatic methods allow us to assemble the pieces. 

Bioinformatics can also be used to guide drug design experiments and maximize the chances of finding active molecules. This new knowledge can eventually be used to develop therapies and vaccines to save human lives. Here, we will look at some examples of how we can use bioinformatics to discover molecular signposts for particular biological processes. These signs are known as biomarkers, and they are important in all types of clinical research. We will then take a closer look at how bioinformatics can use this information to come up with an application, such as a drug.  

Biomarkers of regeneration

Humans do not have the ability to regenerate limbs after amputation, but certain animals have this extraordinary ability, including planarian flatworms and axolotls. To understand these strong regenerative capabilities, scientists study fruit flies, flatworms, axolotls, and zebrafish. These species are powerful model systems to study tissue regeneration after amputation or damage. As in most biological fields, modern-day bioinformatics techniques are playing a key role in understanding how the genome responds to injury. 

Regeneration requires a real-time genomic response, which can be studied by looking at which genes are activated or repressed in individual cells with single-cell RNA sequencing. A recent study from Fincher et al. identified flatworm genes that were active after injury by analyzing all messenger RNA (the transcriptome) of individual lineage precursor cells with Drop-seq. This technique isolates single cells in droplets so that they can be separately analyzed and compared. This method is so powerful that researchers were able to detect the transcriptome from cell types with frequencies as low as ~10 cells per animal³.

Bioinformatic analyses allowed the cells to be clustered by gene expression groups in different tissue types, which then allowed researchers to build an atlas of genes expressed in the transcriptome after injury. 

In another example, Vizcaya-Molina et al. identified novel enhancers that regulate gene activation during different phases of recovery from injury in developing fruit flies. The researchers looked for accessible regions in the DNA (which are associated with higher gene activation) using a technique called ATAC sequencing. They confirmed that some regions of the transcriptome changed in response to injury, and they then wanted to know if those genes had common functions. With the help of bioinformatic databases, they found that many of those genes belonged to signaling pathways involved in cell growth and differentiation⁴. 

A study by Goldman et al. uncovered the genetic regulatory program that responds to injured cardiomyocytes in zebrafish. Inaccessible regions of DNA are tightly wrapped around proteins called histones. They looked at profiles of a replacement histone that indicates transcriptional accessibility, known as H3.3, to uncover gene regulatory elements involved in heart regeneration. This method allowed researchers to identify genes that were upregulated in response to injury. Later, during cardiomyocyte regeneration, they found an enrichment of enhancer elements that were “open” for transcription and then identified the specific sequence involved during regeneration⁵.

These examples show that bioinformatics helps to unlock the mysteries of genes that regulate regeneration after injury. Bioinformatics techniques are applicable to monitoring  real-time genomic response in individual cells, probing sections of accessible regions in the DNA in several organisms that are capable of regeneration. The greater computational power that bioinformatics provides will allow scientists to ask new questions that are important to the field of regeneration.  

Biomarkers of virulence factors

Bioinformatic tools are also important in finding biomarkers of infectious disease virulence, which can be appealing candidates for drugs. For instance, we can look for specific genes that drive the pathogenicity of a given microorganism, such as yeast. To do this, we can design strains that lack particular genes and evaluate if this makes them less pathogenic. Testing a large number of yeast strains is typically performed using competitive growth methodologies⁶. For example, Han et al. evaluated growth of each mutant strain under controlled conditions of direct competition with other mutants, thus reducing the time and cost associated with screening each one individually. This enabled screening of a large number of strains to identify a drug target. 

An example of how functional genomics can be used to identify drug targets in pathogenic fungi has been carried out in Candida albicans with the C. albicans fitness test (CaFT). In this test, each isolate is assigned a unique identifier (barcode) that we can track computationally in order to observe if there were differences in fitness among heterozygote isolates. This enabled the researchers to screen for loss of gene function in the presence of antifungal agents, from which they identified the mechanism of action of novel compounds⁷.

Competitive fitness profiling was also used to evaluate the relative fitness of large pools of A. fumigatus mutants to identify those that are involved in virulence using a non-genetically barcoded library of mutants⁸. As a result, they reduced the total number of animals that are usually required to perform virulence screening. Tn–Seq is another technique used to assess the contribution of genes to fitness in Streptococcus pneumoniae. However, instead of deleting the gene, Tn-Seq inserts additional DNA within the gene⁹.

Similarly, changes in mutant frequency can be used to compare the fitness of the different mutants. By looking at which mutants grow most poorly, scientists can identify which genes are the most essential and consider them as potential drug targets. This is of particular interest in drug discovery programmes, since it is crucial to identify genes that are responsible or involved in pathogenicity to develop and design a novel therapy.  

Drug design

Once we have found the optimal drug target, we can turn to bioinformatics again to help us find a drug for it. A classic approach is to generate millions of molecules experimentally, test them, and register the ones that have an effect. However, this method is very time-consuming and resource-intensive, while the number of effective molecules can be low. Instead, we can use our models of molecular interactions to test molecules computationally and only test experimentally the ones that are predicted to be effective. This allows us to narrow down the set of molecules to test in an experiment while maximizing the chance of success. Indeed, Doman et al. showed that computational tests increase the efficiency of these experiments. When they screened a big library of molecules, only 0.02% of their tests were positive. However, when they used a computational analysis to  evaluate only the ones predicted to be effective, 35% of their tests were positive¹⁰. Thus, virtual screening saves a considerable amount of time and money by reducing the number of assays yet results in higher efficiency. In fact, there are several examples of drugs found through computational screening that have been approved by the FDA. These include dorzolamide to treat glaucoma, captopril to treat hypertension, and saquinavir to treat HIV¹¹. Moreover, these approaches are being used in the context of the current COVID-19 pandemic to find potential new treatments.

All potential drugs should be subjected to multiple stages of evaluation to assess their safety—first in preclinical tests with model organisms, and then in clinical studies in humans. Despite the promise of computational methods to help identify active molecules, most fail to pass these clinical studies because of unwanted side-effects. Thus, one of the newest endeavors in the field is the use of machine learning to add predictions on how likely a given molecule is to be toxic. Machine learning is a series of tools that find trends in known data to predict the results of future observations¹².

Currently, these methods look at databases of molecules to extract their physical properties and health concerns associated with them. Then, they build models that link those properties to health concerns to derive general rules. These approaches have been very successful, with some models being able to identify toxic compounds with up to 95% accuracy.

Gaining access to greater computational power has allowed us to pursue new questions and develop further techniques to address them. This has had a notable impact on diverse fields, from basic science to applications in the clinic. The future of bioinformatics will certainly be exciting, as it will likely produce more and more results that have an impact on our daily lives.

References:

1. Edgar, T. W. & Manz, D. O. Research Methods for Cyber Security. (Syngress, 2017).
2. Gauthier, J., Vincent, A. T., Charette, S. J. & Derome, N. A brief history of bioinformatics. Brief. Bioinform. (2018). doi:10.1093/bib/bby063
3. Fincher, C. T., Wurtzel, O., de Hoog, T., Kravarik, K. M. & Reddien, P. W. Cell type transcriptome atlas for the planarian Schmidtea mediterranea. Science 360, (2018).
4. Vizcaya-Molina, E. et al. Damage-responsive elements in Drosophila regeneration. Genome Research 28, 1852–1866 (2018).
5. Goldman, J. A. et al. Resolving Heart Regeneration by Replacement Histone Profiling. Dev. Cell 40, 392–404.e5 (2017).
6. Han, T. X., Xu, X.-Y., Zhang, M.-J., Peng, X. & Du, L.-L. Global fitness profiling of fission yeast deletion strains by barcode sequencing. Genome Biol. 11, R60 (2010).
7. Xu, D. et al. Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans. PLoS Pathog. 3, e92 (2007).
8. Macdonald, D. et al. Inducible Cell Fusion Permits Use of Competitive Fitness Profiling in the Human Pathogenic Fungus Aspergillus fumigatus. Antimicrob. Agents Chemother. 63, (2019).
9. Solaimanpour, S., Sarmiento, F. & Mrázek, J. Tn-seq explorer: a tool for analysis of high-throughput sequencing data of transposon mutant libraries. PLoS One 10, e0126070 (2015).
10. Doman, T. N. et al. Molecular docking and high-throughput screening for novel inhibitors of protein tyrosine phosphatase-1B. J. Med. Chem. 45, 2213–2221 (2002).
11. Sliwoski, G., Kothiwale, S., Meiler, J. & Lowe, E. W. Computational Methods in Drug Discovery. Pharmacol. Rev. 66, 334–395 (2014).
12. Yang, H., Sun, L., Li, W., Liu, G. & Tang, Y. In Silico Prediction of Chemical Toxicity for Drug Design Using Machine Learning Methods and Structural Alerts. Front Chem 6, 30 (2018).

The authors:

Adelita Mendoza

Angel F. Cisneros Caballero

Anna Bajur

Narjes Alfuraiji

In late 2019, Thomas Merritt approached the members of the Communication & Outreach Subcommittee of the GSA Early Career Leadership Program about submitting a proposal for The Allied Genetics Conference (TAGC) 2020. The members of the subcommittee jumped at the opportunity, and a group of six submitted a full proposal, which the Genetics Society of America accepted for an in-person workshop. 

Then, COVID-19 happened, and GSA made the difficult choice to cancel the in-person conference. However, a few weeks later GSA announced that TAGC 2020 was pivoting to a fully virtual format. The conference would now have free registration, and each accepted workshop was offered a virtual workshop spot using Zoom. 

Once again, the Communication and Outreach Subcommittee team jumped at the new opportunity to showcase science communication and outreach to a virtual audience. We met weekly to discuss the new format and were thrilled to contact representatives from other Early Career Scientist Subcommittees, who graciously volunteered their time to serve as panelists. In addition to Communication and Outreach Subcommittee members, Amanda Shaver and Michelle Jonika joined us from the Career Development Subcommittee, and Malgorzata (Gosia) Gazda joined us from the Steering Subcommittee. 

The Science Communication: Challenges and Impact Workshop was the first featured workshop at The Allied Genetics Conference Online 2020. Our objective was to provide a diverse group of panelists who could discuss their specific experiences in science communication and outreach, as well as provide a space for scientists to discuss different approaches to science communication. 

The workshop consisted of three parts: a panel discussion, an activity with the participants, and a Q&A session. Our panelists opened the workshop by sharing their experiences with diverse platforms for science communication. While our panelists spoke, our participants engaged in a lively discussion using the Zoom chat feature to share their own recommendations, experiences, Twitter handles, and countries of origin. Some of our participants also live-tweeted the event using the #GSASciComm hashtag, and our co-moderators engaged with these Twitter conversations live during the workshop. 

After each panelist spoke about their experiences, we split the participants into breakout rooms with one panelist as the room moderator for a guided activity. Participants were provided with an excerpt from a scientific paper prior to the workshop for this activity, and spent 15 minutes discussing how to explain the excerpt to broader audiences.

Excerpt:  

“We then found that a short region of RNA-dependent RNA polymerase (RdRp) from a bat coronavirus (BatCoV RaTG13)—which was previously detected in Rhinolophus affinis from Yunnan province—showed high sequence identity to 2019-nCoV. We carried out full-length sequencing on this RNA sample (GISAID accession number EPI_ISL_402131). Simplot analysis showed that 2019-nCoV was highly similar throughout the genome to RaTG13 (Fig. 1c), with an overall genome sequence identity of 96.2%. Using the aligned genome sequences of 2019-nCoV, RaTG13, SARS-CoV and previously reported bat SARSr-CoVs, no evidence for recombination events was detected in the genome of 2019-nCoV. Phylogenetic analysis of the full-length genome and the gene sequences of RdRp and spike (S) showed that—for all sequences—RaTG13 is the closest relative of 2019-nCoV and they form a distinct lineage from other SARSr-CoVs (Fig. 1d and Extended Data Fig. 2).”

Reference: Zhou, et al., 2020. Nature. 

Finally, we began the Q&A session with questions that our participants submitted during registration, then opened the floor for other questions from the participants. 

We are proud to report that the workshop was a great success! We brought together a total of 70 highly motivated participants from at least 15 different countries. Our participants eagerly engaged in the discussion by asking questions and sharing their own experiences, which continued on Twitter with the #GSASciComm hashtag. In fact, there was so much to discuss that the workshop extended for an hour longer than originally planned!

There are definitely improvements we would like to make for next time—and we would love for there to be a next time! Participants submitted valuable feedback and we will incorporate several of these suggestions in future plans and proposals, including longer breakout sessions (in a virtual format) and possibly including other languages in our breakout room sessions. 

Survey testimonials

“I really appreciated hearing how the panelists got started in science communication and hearing about all the different resources available (virtually none of which I’d heard of before).”

“The ‘face-to-face”’ of the break-out session was really nice. To actually have conversations with people ‘at a conference’ was really awesome, especially given the current climate.”

“Thanks to the organizers and panelists for this event! Planning a panel in a limited time during physical distancing is very challenging (since I am also involved in planning career development panels in my university). It was a well-planned and motivating panel. Sharing your experience was very valuable during these times. I would love to hear more about further workshops or journal clubs.”

“This was a great group of organizers and panelists that energized and inspired the participants.”

Check out the Communication and Outreach subcommittee’s SciComm Resource Guide. 

Engage with us on Twitter using the #GSASciComm hashtag.