Kylia Williams – The Early Career Voice

Whole Exome Sequencing of Congenital Heart Disease Patients in Sub-Saharan Africa

May 10, 2021May 7, 2021 Kylia Williams

My research is on the genetics of congenital heart disease (CHD), and although it is one of the most common birth defects, the genetic causes of most cases are unknown. So I’m always interested to read new papers on the topic to see how different groups are addressing the problem and to find new candidate disease genes to look into.

A group at the NIH led by Dr. Paul Kruszka recently published a paper in Circulation: Genomic and Precision Medicine titled “Exome Sequencing and Congenital Heart Disease in Sub-Saharan Africa”. The authors begin by pointing out that while there are many studies using whole-exome sequencing to identify genes associated with CHD, these cohorts are primarily made up of patients of European descent. However, CHD and the pathogenic variants that cause it do not discriminate based on ethnicity. This group sought to help fill the gap in research on non-syndromic CHD cases in sub-Saharan Africa.

Using data from 98 trios of patients and their parents, they identified de novo variants (found in a patient but not their parents) or singleton variants (found only in one patient) in 9 genes known to cause CHD. They also identified several very rare protein-truncating variants in 5 known CHD genes and 3 novel candidate genes that are predicted to be intolerant to loss-of-function. They functionally tested high-interest candidate genes in knockout Drosophila models, as they have similar cardiac developmental networks to humans. These experiments identified 4 genes that resulted in elevated fly mortality which were not previously associated with CHD (UBB, EIF4G3, SREBF1, and METTLE23).

For me, the main takeaway from this paper is tied to its limitations of small sample size and lack of a control population for testing variant burden. We need to focus on creating diverse and representative patient and control cohorts in sequencing studies to identify novel disease-causing genes and pathways and prevent misclassification of variants. In accomplishing that, our research can be as meaningful as possible to as many patients as possible.

References

Ekure EN, et al. Exome Sequencing and Congenital Heart Disease in Sub-Saharan Africa. Circulation: Genomic and Precision

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”

Art in Science

February 24, 2021February 23, 2021 Kylia Williams

In 2020, my resolution/quarantine hobby was learning how to draw and paint. The year before, I had to make a figure for a review paper, but I was paralyzed for weeks because I didn’t know what to make, and I thought I was bad at drawing. Determined not to let that happen again, I started figure drawing and soon delved into the intricacies of portraying plants and animals in watercolor. It reminded me of the botany class I took in college where every week we trekked through the Illinois forest and made anatomically accurate sketches of the plants we saw.

Art and science have always gone hand in hand. Leonardo da Vinci was skilled in dissection and was one of the first to create detailed drawings of the human heart and describe coronary artery disease. Current science and medical illustrators use a mix of photorealism, illustrative diagrams, and data visualizations as teaching tools. Other times, art is used to tell a story or promote the public interest, as Ashley Cecil did during her time as artist-in-residence at the Carnegie Museum of Natural History and the Richards-Zawacki lab at the University of Pittsburgh.

Illustrations have been essential during the COVID-19 pandemic, starting with the spiky blob that has been the face of the virus. Everywhere we go, there are images of proper mask-wearing, hand-washing, social distancing, COVID-19 symptoms to watch for, nasal swab testing procedures, and now, vaccination information. Data visualizations (less artsy) such as the Johns Hopkins COVID-19 dashboard have also helped us to keep track of infection trends.

CDC/ Alissa Eckert, MSMI; Dan Higgins, MAMS

Although text and graphs get the point across, there are many opportunities for scientists and physicians to incorporate illustrations:

When you want to grab or keep people’s attention. Even simple graphics can add humor and visual interest.
When talking to people outside of your field. People may not know the same jargon that you do, it can be easier to convey information with images.
For complex ideas, pathways, and processes that are difficult to digest with long, dense paragraphs. Graphical abstracts are also becoming a more popular way to summarize papers.
When photographs are too detailed or not possible to take. Anything from a simple sketch to a full color drawing can fill the void.
For emphasis. Some points may need to be repeated in different formats.

For future papers and presentations, I’ll be less hesitant to incorporate illustrations of my own. Even if you don’t consider yourself an artist, images and illustrations are freely available from sites such as Smart Servier Medical Art or the CDC’s Public Health Image Library. Or make drawing your newest hobby, too, to gain a greater understanding of your work and the world around you.

The Power of Representation

January 27, 2021January 26, 2021 Kylia Williams

On January 20th, Vice President Kamala Harris was sworn into office, becoming the first woman, African American, and Asian American to hold the position. Just two weeks earlier, Reverend Raphael Warnock and Jon Ossof became the first African American and Jewish senators, respectively, to represent my home state of Georgia. In addition, President Joe Biden has committed to the most diverse Cabinet in history, with about half of his nominees being women. If you have always had a plethora of examples of people who look like you and share your story, you may not understand why this is such a big deal. For the first time, millions of Americans (including myself) are seeing themselves represented at the highest levels of government. This got me thinking more about how representation affects us because having diverse representation, particularly in government and media, is important for establishing how others see us and how we see ourselves.

While diversity is about who is allowed in certain spaces, representation is about who is given a voice and the opportunity to tell an authentic story. These voices and portrayals affect how groups of people are perceived by others and define what issues are deemed important. Lack of representation does not simply mean that there is a lack of diversity, but that diverse voices go unheard and contributions go unnoticed. When there is a gap in representation, those gaps are filled by our preexisting biases about what people are like and who can hold certain roles. If we have no exposure to other people’s stories, how can we empathize with them?

When you see portrayals that feel true to your life and that of those around you, it expands the horizon of what you feel is possible because you can only be what you can see. And as actor Riz Ahmed said, “we all want to feel seen and heard and valued.” Lack of representation can lead to imposter syndrome, which I wrote about in a blog post in November. If we don’t see people we identify with doing something, we may not feel that we can do it. And if no one values contributions from people who look like us, we feel like no one should value ours.

**There is an encore webinar on Imposter Syndrome at AHA International Stroke Conference 2021 on 3/17, you can register for the conference here**

There are a few traps to avoid when thinking about representation. Tokenism occurs when we expect one person to be the voice of an entire group of people, and stereotyping occurs when we oversimplify our representation of a group of people. Often, portrayals of minorities, especially Black people, are in the role of the victim. While these can be important, victimhood does not encompass the full lived experience of most minorities. All of these pop up when diversity is lacking, and when we don’t acknowledge that even within a group of people, there is an infinite number of individual experiences.

Aside from the recent progress in public politics, there are many examples of good representation in the media. That list is ever-growing, and these positive representations have noticeable effects. The character of Agent Scully on The X-Files, an FBI agent, and medical doctor, prompted an increase in the number of women studying and working in STEM fields, a phenomenon coined “The Scully Effect.” Doc McStuffins, the Disney Junior show about a Black girl who is a doctor for toys and stuffed animals, was a hit among children and adults, helping kids get over their fear of going to the doctor and leading to members of the Artemis Project starting the We Are Doc McStuffins campaign to inspire more future doctors. In current news, women of color have been widely sharing photos and videos of themselves being vaccinated against COVID-19 to help overcome the deep mistrust of medical institutions, which Dr. Aubrey Grant wrote about in a previous blog post. Also, be on the lookout for Dr. Mary Branch’s upcoming blog post with more on diversity and representation in medicine.

I’m assuming that most people reading this aren’t in the fields of politics or television, but you don’t need a public office or a prime time slot to promote representation. Everybody has a platform, whether that be in-person conversations with friends or a Twitter following. You can use your platform to promote other voices, especially those of people more marginalized than you or when addressing issues that you do not have personal experience with. Also, think about whether there is an issue that could use your voice or a story that you can authentically tell and be that representative for others.

COVID-19 Changing Clinical Trials

December 30, 2020December 28, 2020 Kylia Williams

This year was the first time I’ve attended the AHA’s Scientific Sessions, and although I didn’t get the full experience in a busy conference hall, the virtual experience did have some advantages. I was able to attend every session that interested me, either live or later on demand. In-person discussions were substituted with Zoom rooms, and Twitter threads allowed me to interact with people I may not otherwise have seen. I also liked that I could see all the sessions and posters that are available at a glance. When looking at the schedule, I noticed how much focus Scientific Sessions places on clinical trials and was surprised by the number of variety of ongoing trials.

Before Scientific Sessions, my knowledge of clinical trials was limited to the information in the AHA’s “A Guide to Understanding Clinical Trials”. I learned a lot by watching the various talks, late-breaking science presentations, and “Meet the Trialist” Q&A sessions. I also appreciated that these presentations focused not only on positive results of interventional trials but also on the results of null trials as well as implementation trials focused on care delivery. Several other early career bloggers have written blog posts about the individual trials covered at Scientific Sessions. What interested me the most was the intersection of clinical trials and the COVID-19 pandemic.

Dr. Clyde Yancy stated that “we cannot partition the social experience from the scientific reality, because they are intertwined.” COVID-19 has made this fact especially clear, as science is at the forefront of the public conversation and the social disparities in science and medicine are stark. During the Opening Session, two giants of cardiovascular medicine, Dr. Eugene Braunwald and Dr. Nanette Wenger, along with Dr. Yancy and Dr. Robert Harrington discussed some of these issues in the context of clinical trials and the changes that have been brought about or accelerated by COVID-19.

One important change has been the increase in public-private partnerships and the sharing of data between groups. Dr. Wenger noted that in some fields, there has already been the development of consortiums, large networks of study sites, that are consistently maintained so that large trials can be started efficiently. The prevalence of these is only growing as the benefits of data sharing are becoming more obvious.

They also discussed the increase in clinical trial enrollment during the pandemic. Dr. Braunwald noted that there has been an increase in scientific literacy among the general public, and people know more about clinical trials. They also acknowledged the expansion of telehealth, including video visits, virtual consent, remote monitoring, and the inclusion of patient-entered data, which makes it easier for participants. There has also been a streamlining of protocols, leading to COVID-19 vaccine trials to be conducted with unprecedented speed and allowed the continuation of other current trials.

These changes have led not only to an increased number of study participants but also greater diversity. There tend to be gender and racial disparities among participants of clinical trials, but virtual platforms reduce the cost associated with study participation. However, Dr. Wenger made it clear that minority populations remain underrepresented; trial populations for COVID-19 still do not reflect those most affected by the disease. During the Closing Session, Dr. Norrina Allen discussed some of the population science research presented at Scientific Sessions, showing that racial disparities in health can be attributed to social and environmental drivers. She emphasizes that one way to narrow these gaps and increase diversity in trial enrollment is to increase the diversity of research teams and clinical trial leaders. This has been a thread throughout all of the Scientific Sessions – that diversity and inclusive environments in science and medicine leads to greater equity and better health for all.

Setting Expectations for AI Models in Medicine

November 18, 2020November 17, 2020 Kylia Williams

Artificial intelligence is a hot topic in every field, and these algorithms are being widely used in scientific research. Particularly in my field of genetics and genomics, machine learning methods are invaluable for gleaning insights from large amounts of highly dimensional data. But there are many things to consider before applying AI and ML in a clinical setting, when real people are on the other end of the predictive model. It is important to set expectations for what AI can and cannot accomplish and what is needed for a broad application of AI in medicine in the future. In the session “Hype or Hope? Artificial Intelligence and Machine Learning in Imaging”, presenters gave a great overview of the applications of AI, its limitations, and the advancements that are needed for a wide application of AI in medicine.

Dr. Geoffrey Rubin described many different scenarios in which AI can be deployed. Specifically, he talked about how AI can be used in predictive analytics to make test selection and imaging more efficient, in image reconstruction to reduce noise, in image segmentation to identify regions of interest and provide quantitative analysis, and in interpretation to derive unique characteristics that cannot be measured directly, identify abnormalities, and create reports. In addition, Dr. Tessa Cook explained in greater depth how AI can be used as clinical decision support to incorporate diverse data types and aid in proper test selection. Dr. Damini Dey also discussed how AI can improve diagnosis and prediction, characterize disease, and personalize therapy. Overall, it is important to determine where AI can provide the greatest value while introducing the least amount of risk.

However, there are many limitations to AI and ML models. First, as Dr. David Ouyang noted, because these models are trained by humans, they can only perform tasks that a human could theoretically do. AI just performs these tasks faster, more consistently, and at a larger scale. He noted that these models are not effective unless trained on broad underlying datasets, and that unless explicitly programmed, they do not accurately weight rare significant events. AI models can easily become uninterpretable black boxes, keeping experts from recognizing where they are failing. Dr. David Playford emphasized that due to these and other limitations, AI models are not yet clinically accurate in all areas.

There are many steps that must be taken before AI models can achieve wide use in clinical settings. Dr. Ouyang suggests standardized baselines and open access to measure advancements among tools. Dr. Cook implements a “trust and value” checklist to assess how each tool was trained and tested, as well as what it can and cannot do, before using it for clinical decision support. Dr. Playford advocates for randomized trials to establish proof-of-concept and compare outcomes to the current standard of care. Most importantly, steps must be taken to reduce bias in AI models, which can negatively impact the care of underrepresented populations. Multidisciplinary collaborative teams can ensure that the data aligns with the clinical question being tackled, diverse yet consistent training datasets are being used, and methods such as transfer learning are implemented to produce more accurate predictions on previously unseen datasets. While AI can be an important tool in clinical decision making, it is ultimately the responsibility of each physician to ensure that AI tools are serving their patients as effectively as possible.

Overcoming Imposter Syndrome

November 14, 2020November 14, 2020 Kylia Williams

This year’s AHA Scientific Sessions has a strong focus on racial and gender diversity and equity, as well as creating inclusive environments in science and medicine. It is great to see that there are increasingly more opportunities opened up to people who are traditionally underrepresented, but there are still challenges that are faced when we get there. One discussion that really interested me focused on one of those challenges: imposter syndrome.

Imposter syndrome is an internal struggle. It is the inability to recognize your own success; the feeling that you don’t belong somewhere and will soon be outed as a fraud. As a Black woman and the youngest person in my PhD cohort, it is a feeling that I have felt too many times to count. Imposter syndrome can cause you to self-sabotage by not applying to opportunities, missing deadlines, or avoiding networking because you feel that you do not belong in that space. The panelists today – Dr. Toniya Singh, Dr. Gina Lundberg, Dr. Aaysha Cader, Dr. Ambreen Mohamed, Dr. Aamisha Gupta, Dr. Janet Han, and Dr. Nasrien Ibrahim – discussed the ways in which we can overcome imposter syndrome and reach our fullest potential.

When feelings of inadequacy first appear, it is important to recognize that feelings are not fact. Dr. Gupta stresses defining the facts by listing your accomplishments and qualifications. Reframe your thoughts to center everything you contribute instead of the credit you think you should get. Women, in particular, tend to underestimate themselves, so it is helpful to have a diverse circle of friends and allies that can be honest with you, encourage you, and advocate for you to others. If you have the means, having a career coach can help you to focus on your goals while providing honest and objective feedback on strengths and weaknesses. It is an invaluable investment in yourself. Imposter syndrome can also make public speaking difficult. Dr. Lundberg suggests focusing on presenting for one specific person instead of a large audience. Remind yourself that you are the expert here and that everyone who is watching wants you to be yourself and to succeed.

Regular self-reflection can help quickly overcome imposter syndrome in the future. Dr. Cader emphasizes aligning your behaviors with your values so there is no dissonance between what you are doing and what you want. Finding intrinsic value in the things that you do can make it easier to recognize your achievements. When you put time into doing what you love, you can’t help but dream big. This panel reminded me that imposter syndrome is something many people go through and that you can experience it and still be successful. Talking about your experiences can help everyone overcome this challenge so that when opportunities arise, we don’t hesitate to take them.