Investigation of Neural Networks’ Capabilities for Gene Expression Analysis By Hanze (Louis) Wu

1 Introduction 

Recent advances in genetic testing have found novel ways of mapping out an indi vidual’s gene expression. Microarrays, biotechnological chips used for creating graphical representations of gene expression levels, are tools that have led to countless groundbreaking discoveries about the human genome. Visualizing the unique and intricate chemical struc ture of an individual’s genetic profile, microarrays offer an optimal gateway to diagnosing genetic diseases. 

A genetic profile refers to information about specific genes, including variations and gene expression in an individual or a certain type of tissue. Gene expression involves the transcription of information inside DNA into coding or non-coding RNA sequences (ncRNA). In the case of diseases like cancer, mutations in the original DNA genes lead to harmful changes in protein production and ncRNA behaviour. Protein production can be altered by the transcription of mutated mRNA sequences, leading to up/downregulation of gene products, or malfunctioning sets of certain proteins. Meanwhile, defective ncRNA can lead to adverse epigenetic side effects, such as gene silencing or DNA methylation. 

The method of gene analysis chosen in this paper is non-coding RNA profiling by array, which involves the extraction of ncRNA sequences (especially miRNA) from tissue. ncRNA sequences account for 98% of the human genome, making reverse transcription into DNA sequences possible. The transcribed DNA sequences are then put through microarray analysis, which involves the detection of targeted gene sequences through microscopic probes 

 

and a comparison to a control gene profile using coloured fluorescents (figure 1). The result of microarray analysis is a graphically represented profile of an individual’s normal and abnormal levels of expression in each gene. Though too complex for human analysis, the differences between gene expression levels in healthy individuals and cancer patients can be analyzed with the use of artificial neural networks, a computer representation of the brain. 

2 Procedure 

A massive database full of labelled gene expression data was vital for reliable AI train ing. Fortunately, the GEO (Gene Expression Omnibus) database, maintained by the NCBI had thousands if not millions of labelled hybridization arrays, chips, and microarrays. 

However, most datasets consisting of Homosapien genetic expressions only had up to a thousand microarray samples, insufficient for deep learning. To obtain a sufficient quantity of data, labelled microarrays from a massive 2018 research project with the title, Integrated extracellular microRNA profiling for ovarian cancer screening, was used. This database provided not only 40,000 patients’ miRNA profiles, but also labelled them with 12 different types of cancer, and a non-cancer label based on future diagnoses. Using GEO’s API, 4 large datasets from this experiment, totalling up to 13,000 microarrays were processed in series matrix format. 

To analyze the learning progress of the AI, 10% of the dataset was allocated for valida tion. Afterwards, a multilayer perceptron neural network was created to fit the data. Unlike convolution-based models where the inputs are downscaled for general pattern recognition, this model analyzes each input neuron independently from its neighbours, making it more fitting for the task of complex gene expression analysis. 

Overall, this model had 1,186,825 trainable parameters. To prevent overfitting, and to help it learn faster, 5,024 non-trainable parameters consisting of dropout layers and batch normalization layers were implemented. The dropout layers had a 30% dropout rate, meaning that on each iteration, 30% of the neuron connections were cut, making it near-impossible for them to overfit the training data. The batch normalization layers simply scaled each layer to have a unit standard deviation, making the data easier to work with. 

Each layer of the network used the ReLU (rectified linear unit) activation function to preserve neuron activations. The output layer used the Softmax activation function to convert the vector of activations into a vector of probabilities. This output vector represented the network’s confidence in the presence of each of the 13 labels. 

3 Results 

As visible from figure 2, the perceptron model started with an accuracy of less than 60% and ended up having 98% accuracy on the training dataset while having 93% accuracy on the validation dataset. This indicated that the AI did not overfit the training data, and can reliably perform a cancer diagnosis on a Homo sapien microarray sample. 

 

pre dictions while the vertical axis represents the doctor-diagnosed values. It is above 90% accurate on 11 of the 13 labels. However, due to the small amount of glioma microarray samples provided in the dataset, it is only 36% accurate in classifying it and confuses it with lung cancer samples. 

For the purpose of data visualization, the microarrays were converted to 45 by 57 images, representing each gene’s expression within a green to red scale. Figure 4 shows 8 randomly selected microarrays diagnosed by the AI. Within these diagnoses, the AI’s median certainty for a specific type of cancer is 99%. 

4 Conclusion 

Artifical Intelligence’s pattern recognition of miRNA expression levels is extremely ac curate and is a powerful tool for conducting genetic disease screening, along with other forms of gene expression analysis. With the 93% accurate machine learning model presented in this paper, medical professionals can automatically analyze genetic samples for the diagnosis of 12 cancers, and work with an ever-increasingly reliable second opinion. Furthermore, the success of the program proves the presence of distinguishable patterns in genetic expres sion amongst different cancers. Differential gene analysis techniques combined with the AI’s readings can provide meaningful insight into the specific combination of genes responsible for cancers. 

New Clinical Trial For Type 1 Diabetes Involving Stem Cells by Lynsey Moses

In 1921, a hormone in our body called insulin was discovered. Insulin is a hormone that regulates our body’s glucose (sugar levels). Type one diabetes is an autoimmune disorder where the body will attack a type of insulin-producing cell called beta cells. The most common treatment for type one diabetes available right now is a closed-loop artificial pancreas system. This is a system that automatically injects the patient with insulin. Recently there was a clinical trial for a new technology involving stem cells that could treat type one diabetes. The hope is that this treatment will be more reliable and trustworthy than the current technology available. As great as the closed-loop system is, there are a couple of cons that make people hesitant. The two major cons of these systems are the price and putting all your trust into these devices. There’s a good chance that this new stem cell technology will also be expensive, but luckily the implant would only be a one-time payment versus a continuous investment. There is also a fear of relying completely on the multiple devices needed in the system. This fear comes from the fact that if one device were to malfunction there could be severe consequences. 

Clinical Trial 

Dr. James Shapiro, a University of Alberta professor, has found a way to take stem cells and reprogram them into groups of cells called islets that produce insulin, called endoderm cells. Endoderm cells are cells that are typically found in embryonic life, but Dr. Shapiro has found a way to generate them from adult stem cells. 

Procedure 

With the research from Dr. Shapiro and his colleagues, they were able to implant seventeen type one diabetes patients with the generated cells. Of the seventeen patients, some

were given one large implant while some were given multiple small implants. All implants included the generated insulin-producing endoderm cells. The seventeen patients were selected because they fit certain parameters such as age, time since diagnosis, and hypoglycemia awareness. All patients were required to be between the ages of eighteen and sixty-five due to safety concerns, and the average age of the trial was forty-seven. The trial also required that all patients were diagnosed for a minimum of five years. Time since diagnosis ranged from eight years to fifty-two years. The last demographic of the patients was their awareness of hypoglycemic symptoms, which was measured via their Clarke score. These demographics, along with a few others, were selected to assess how the implant may affect different type one diabetics. 

Results 

The results of the clinical trial provided a lot of hope that there could be a new treatment for type one diabetes. Most of the patient’s bodies reacted well and accepted the implants. These patients were monitored often but had two main examinations at six months and twelve months. After six months, six patients or 35% of the trial showed signs of naturally produced insulin following meals. After a year, eleven patients or 65% of the trial had evidence of natural insulin production daily. 

Adverse Events(AEs) 

Within the first twelve months after the patients were given the implants, there were a total of 297 adverse events recorded. An adverse event is an unexpected physical or mental medical occurrence that happens after an immunization, procedure, or treatment. The adverse events were classified based on severity and causes.

Risks and Next Steps 

The largest risk of the artificial islet currently is that there is not enough data to predict how different people’s bodies are going to respond to the implant. This is proven by the fact that there were multiple different kinds of AEs and multiple different severities. There is also no current data to see what the continuous or long-term effects of this transplant are if any. The next step for Dr. Shapiro and his colleagues would be to collect more data by continuing to monitor the original seventeen patients as well as conducting another trial. This would be

beneficial because there would be more data to prove the effectiveness of the transplant. Conducting another trial would also provide data that could be used to determine if the implant is only successful for a certain group of people, for example, it may work better on a group of younger people versus an older group. Another step that Dr. Shapiro may consider is seeing if the implant could be successful without the use of immunosuppressants or anti-rejection drugs,commonly given to transplant patients to target white blood cells and weaken their immune systems. This helps type one diabetes patients to accept the implant as well as produce insulin. This would be a useful next step because if the implant could be successful without the use of immunosuppressants, it would become a lot safer for type one diabetics, who are often told to avoid immunosuppressants since they already have a somewhat compromised immune system. 

In conclusion, the research and clinical trial which was done by Dr. James Shapiro involving artificial insulin-producing islets derived from adult stem cells have provided hope that in the near future there will be a “cure” or a more reliable treatment for type one diabetes. The results from the clinical trial were promising as eleven patients naturally produced insulin after a year with the implants. However, because of the high amount of adverse events and lack of consistency throughout the results, the transplant is not clinically relevantyet!

When food eats us?

When you think of a tropical fruit, what comes to mind? Perhaps a mango? A banana? A papaya? Like many people, you might have said pineapple, one of the most recognizable fruits with their crowning leaves and spiky skin. Now imagine yourself eating a sweet and juicy pineapple on a hot summer’s day.
Picture the flavours and texture of the fruit on your tongue. Then think of the aftertaste that lingers in your mouth once it has been swallowed. Do you feel a burning sensation in your mouth, a feeling of soreness or a tingle? If you asked these series of questions to anyone who’s ever had a pineapple, chances are they’d agree and say yes. In fact, it happens to virtually everyone, though some maybe more severe than others.

The reason behind this phenomenon honestly sounds like something straight out of a horror film. In short, when you eat a pineapple, the fruit itself is actually… eating you back! Like all fruits, pineapples contain enzymes. However, what differentiates this tropical fruit from others is the enzyme bromelain. Bromelain is a protein-digesting enzyme that is found in most parts of the fruit. When extracted, it can be used as a topical medication, for cosmetic purposes, and as a meat tenderizer. It can aid in the reduction of
inflammation and swelling in the mouth, as well as the removal of dead skin from burns and cuts.

Enzymes are a type of protein that acts as a “fast-forward” button for your cells. They help regulate and speed up the rate at which chemical reactions happen within your body. Without enzymes, the metabolism of a human body would be too slow for anything to function. They also play an important role in digesting the food that you eat. For humans, our stomachs are strong enough to handle bromelain; however, our mouths are not. The inside of our oral cavities is coated with a protective layer of mucous. ( a lining of membrane ). The oral mucus’ job is to act as a barrier between the food/things we put in our mouths. It protects deeper tissues, such as muscle and fat from external dangers. It also contains keratin, a type of protein. And since bromelain is a protein-hungry enzyme, it can start to deteriorate the protective layer of mucus. The enzyme is practically “eating away” at the oral cavity membrane, which therefore causes discomfort.

Not only that, but pineapples can occasionally contain lots of acid (depending on the ripeness), which can also trigger the tongue and create an unpleasant sensation, alongside the decreased
strength of mucus. The good news is, once the pineapple has been swallowed, your stomach acids will burn away the enzymes, halting their reign of terror inside your body.

Nevertheless, there are ways to reduce the amount of bromelain in a pineapple, or direct it somewhere else. For example, eating the fruit with dairy can help divert attention away from the proteins in your mouth and onto those in lactose. Dairy can also help balance out the pH caused by the acidity, toning down the sting. Another method would be to cook the pineapple, which would remove the majority of the enzymes. By heating up the pineapple to a certain degree, the heat will destroy any microbes and enzymes on the fruit, thus “sterilizing” it.

Scientific and medical scheme about enzymes. Enzyme substrates and active sites, chemical and biological processes. Isolated flat enzyme diagram vector illustration.

Nutrition is a vital part of keeping the human body healthy. When we better understand the science behind the food we put in our mouths, it creates a healthier relationship between the mind and food. So, the next time you enjoy a pineapple and feel that slight tingle in your mouth, remember this. Just know that an enzyme by the name of Bromelain is secretly attempting to eat you from the inside out.

The Perfect Chocolate Cake, as Defined by Chemistry by Allison Trieu

Since the simplistic, breadlike, honey-sweetened “cakes” of Ancient Egyptian
civilizations, humanity’s knowledge of cake-making has evolved into the decadent, frosting-smothered desserts seen in bakeries today. However, in order to truly understand how chocolatey sweets come to life, they must be examined at a chemical level. Only then, would it be possible to create a scientifically perfect chocolate cake.

Before an exploration of how to make the perfect chocolate cake may be approached, the definition of the ‘perfect chocolate cake’ must be determined. While this phrase likely means something different to every individual, some characteristics that are widely agreed upon include a fluffy, light texture; a deep, chocolate flavour; a moist crumb that melts in your mouth; and a
silky, creamy frosting to top it all off.

To achieve the first quality, a pillowy texture, multiple factors come into play. Different ingredients are favourable for this outcome depending on the storage of the cake. Oil is the preferred fat in this case, as it is much less dense than butter, which helps the rise of the cake and allows for it to be light. Leaveners are also largely responsible for texture, as sodium bicarbonate in the form of baking powder is essential for the tiny pockets created within the cake. Baking
powder is a complete leavener, meaning that it already contains both an acid and a base, and thus requires only H2O to be activated. The chemical reaction causes carbon dioxide bubbles in the batter, which allow the cake to increase in volume and expand. The type of flour used is also a crucial element to consider; cake flour, which is the preferred type for cake batters, has a protein
content of 5-8%, which results in a softer cake than the 10-13% protein content in all-purpose flour.

Flavour is obviously another essential part of a quality dessert. The flavour compounds of cake coat the taste buds, which allow the eater to experience the taste. When making chocolate cake, bakers often prefer Dutch-processed cocoa, which is cocoa powder that has been alkalized by soaking in a potassium carbonate bath. In this process, the pH of the cocoa powder is increased from about 5.5 in its natural state, to 7 after the alkalization. Dutch-processed cocoa
powder is preferred in traditional chocolate cakes because the more alkaline state of the cocoa powder prevents an imbalance in the acidity that is already neutral, thanks to the neutral leavening power of baking powder. Aside from the chocolate taste itself, there are additional flavourings that are said to enhance this main profile, including vanilla, citrus, and coffee. Fragrance and flavour perception stems from the olfactory bulb at the back of the nasal passage. There are five key flavours that your taste buds can identify: sweet, salty, sour, bitter, and savoury. Usually, these flavours are featured in tandem with each other, like in sour gummies, which are made with sugar for a sweet taste and citric acid for tartness. Featuring an additional flavour in chocolate cake contrasts the very strong, overpowering profile of chocolate; for example, coffee is often used as a ‘secret ingredient’ in chocolate cake, because the bitterness of the coffee offsets the sweet decadence of the chocolate.

A moist, melt-in-your mouth structure is another oft-desired feature in cakes. This element ultimately comes down to the ‘wet’ ingredients used in the batter and the incorporation of the ‘wet’ and ‘dry’ ingredients. If the cake is meant to be stored in the refrigerator or for multiple days, oil is preferable over butter because it has a lower freezing point. It does not solidify when cooled, which would otherwise result in a dry, crumbly cake. When incorporating the wet and dry ingredients, it is crucial to prevent overmixing the batter. Overmixed batter
reduces the air pockets in your batter, which interferes with the structure and deflates the final product. In cakes made with wheat flour, mixing causes gluten strands to form, which is excellent for bread, but not so much for cakes, as too many gluten formations result in a tough dessert. For optimal results, bakers tend to stop mixing immediately once there are little to no dry spots of flour left.

There are hundreds of types of frostings, all made with different methods and of varying difficulties, but one popular one is Swiss-meringue buttercream, which pairs excellently with cakes. Many prefer this frosting because of its airy texture, less-intense sweetness (it does not completely rely on sugar for structure, so it requires less of it), and distinctly buttery taste. Swiss-meringue buttercream is made using egg whites, granulated sugar, and butter, along with
any flavour additives. Using a double-boiler method, the egg whites and sugar are mixed, then heated, allowing for the solid sugar particles to dissolve into the liquid egg whites, which creates a viscous, homogenous mixture. The heat applied to the mixture causes the particles to move faster and spread farther, allowing the two substances to incorporate evenly. This heating also aids the next step, which is whipping the mixture into a meringue; the heat causes the egg proteins to unravel and become easier to whip, as well as melts the sugar into a syrup that stabilizes the air pockets in the meringue. Once your meringue is whipped, butter is added, creating an emulsion in which the egg whites and fat in the butter are being forcibly combined. In the process of becoming a smooth emulsion, the ingredients resist and go through stages of
looking curdled, soupy, and separated, before finally reaching a state of creamy frosting.

At its core, baking is simply chemical reactions and a harmony of flavour compounds. To recognize this and use the precise chemistry behind desserts to improve them guarantees the best tasting sweets possible. Approaching baking with a scientific mindset by always being ready to experiment, make observations, and test out new theories, ensures a lasting success in an individual’s desserts and curiosity surrounding the science behind food.

Why GMOs Should Be More Recognized by Harneet

For thousands of years, humans have used various genetic modification practices to modify the genes of organisms. A genetically modified organism (GMO), is a plant, animal, or microorganism whose DNA (Deoxyribonucleic Acid) has been changed, using genetic alteration methods. One of such
methods includes selective breeding, commonly used in plants and animals to produce organisms with desirable traits.
Selective breeding can be readily observed in daily life, especially in pets, such as dogs with mixed breeds, or the Australian Budgerigar (budgie). This parakeet species is found in a wide spectrum of colours, when the wild budgerigar only exists in yellow and green. In selective breeding, a
breeder selects two parents that have a beneficial trait or physique to reproduce, and develop offspring with those traits of interest. When it comes to wild budgies, they contain both a yellow and blue trait in their genome, which combine to express green feathers; the yellow trait is selectively deactivated, which results in a blue plumage for the species, and a genetically modified organism.

While selective breeding helps to reinforce traits or produce an assortment of plants and animals, it can often be an imprecise process that may create unintended mutations. Nevertheless, with recent advancements in biotechnology, scientists have been able to directly alter the DNA of animals, plants, and microbes. All living things have genes, made up of DNA, which stores our genetic information and determines physical traits, such as feather colour, height, plant type, hair length, etc. When a GMO is created, a gene is inserted into the current set of genes of a recipient organism, which can give it a useful trait like pest resistance. This method is known as genetic engineering, a newer, more efficient way to produce a GMO, as opposed to the traditional and lengthy means of selective breeding. Altering the genetic makeup of an organism can also provide it with beneficial characteristics. For instance, a drought-resistant gene from a plant may be taken and moved into a corn plant, allowing it to withstand droughts. GMOs are also vital in medicine, as they allow researchers to create exceptional inventions that save lives. Bacteria, for instance, have been genetically modified to produce insulin, a hormone that regulates glucose levels and treats diabetes. The human gene for insulin has been inserted into the bacteria’s DNA, allowing it to produce insulin proteins. Today, insulin has saved millions of lives worldwide, showcasing the importance of GMOs for humanity. Moreover, being prominent in the agricultural industry, genetic modification has allowed farmers to grow crops in various parts of the world, produced to be disease and pest resistant, have a longer shelf life, include greater nutrient levels, and taste better. Because GMO crops produce higher yields, consumers will have lower prices to pay, and hunger can be conquered. In addition, many crops are modified to be insect-resistant, hence, farmers can minimize the use of additional pesticides, making GMOs environmentally friendly.

While GMOs bring a number of benefits in the agriculture and medicine industries, they cause immense controversy as well. Many consider them to be unsafe, as genetic engineering alters an organism in ways that would not occur naturally. Others believe that GMO foods have the potential to trigger allergic reactions, as they may contain genes from an allergen. These concerns arise from the lack of education regarding genetically altered organisms and other bioengineering processes, that are, in fact, more common than many people think. One may choose not to purchase a can of corn labelled “GMO”, automatically assuming that it is unsafe. Thus, most suppliers, with a fear of losing profit, don’t label products that have been engineered with microorganisms. However, it is vital to make efforts to spread awareness regarding GMOs and their benefits, which are not only limited to growing more resilient crops that last longer. Labeling such foods is important, as it will increase the understanding and recognition about GMOs; instead of fueling unnecessary fears, it will motivate consumers to learn about basic biology and plant breeding processes, as well as the science behind the foods they eat everyday, recognizing the impacts of genetically modified crops in our daily lives. In addition, labelling genetically altered foods will not only promote awareness about them, but also allow consumers to decide whether or not they wish to eat genetically altered products, as we all have the basic right to decide what we eat.

The only aspect that differentiates a GMO from a normal organism, is the arrangement of DNA; all DNA contains the same building blocks, whether modified or not, hence GMO foods don’t pose any more risk to human health than ordinary foods do. However, it is vital that one is aware of the food they consume, in order to prevent allergic reactions. Although our digestive system breaks down all DNA in the same way, research about GMO foods is still minimal, and little is known about the long term health effects they may or may not cause. While genetically altered crops are not deemed unsafe, it’s important for people to acquire knowledge about the foods they eat; the easiest way to provide this knowledge is by labelling foods that are bioengineered, which can only be done by food companies themselves.

Nevertheless, as biotechnological research continues to advance, more information about genetic engineering is being discovered, and the crops we eat everyday are being modified with beneficial traits. The more that people become educated about such genetically modified organisms, the better it will be for their safety and health. Today, GMOs continue to enhance crop production, and genetically modified animals allow for extensive laboratory research, and will continue to do so as society progresses.

Telephone -A STEM Invention That Revolutionized The World

Alexander Graham Bell once said “The day will come when the man at the telephone will be able to see the distant person to whom he is
speaking.” This quote reflects Alexander Graham Bell’s powerful vision that was once an unattainable dream in the eyes of many people decades ago, which is only possible due to the efforts of the STEM world.

As technological advancements continue to revolutionize the Earth, the fascinating world of STEM is expeditiously growing at an unprecedented rate. Unquestionably, there are many STEM related inventions that have reshaped history. However, one of the most established and greatest STEM milestones is the telephone. The telephone was invented on March 10, 1876 by Alexander Graham Bell through a fascinating breakthrough. The telephone that once required an individual to speak and hear from a small hole using a thumper
has now developed to a digital touch screen phone that allows you to communicate across the globe within seconds. This achievement would never have been possible without STEM (Science, Technology, Engineering, Mathematics), and has radically changed communication throughout the world.

Alexander Graham Bell’s interest in sound technology and mechanism led to the astonishing discovery of the telephone. In 1871, Bell started working on the harmonic telegraph, which was a device that allowed multiple messages to be transmitted over a wire at the same time. While trying to perfect this technology, Bell became preoccupied with finding a way to transmit human voice over wires. By 1875, while discovering how to transmit a simple current, Bell quickly came up with a simple receiver that could turn electricity into sound. Moreover, over time, Alexander’s telephone significantly changed
2 with new developments in tone dialing, call tracing, music on hold, and electronic ringers, showcasing how far the field of STEM has elaborated.

According to a survey conducted in the US, 60% of America’s economic growth depends on STEM growth. Furthermore, since 1990, jobs in STEM
have grown by 79% highlighting the increasing demand of STEM in many job sectors. Without competent STEM professionals such as Alexander
Graham Bell, there would be no emerging technological advancements, discoveries and inventions, and as a result, the world could come to an end! The science and mechanism used in the invention of the telephone led to several other inventions such as the telegraph, the transatlantic cable, the phonograph, and radio technology. STEM is such a broad and fascinating field that is quickly revolutionizing our world by sharing an emphasis on innovation, problem-solving, and critical thinking which is creating a popular, and fast growing industry.

In my opinion, it is truly important to acknowledge the various STEM inventions that have significantly benefited our world as STEM technology allows our youth to work in a challenging environment equipped with high tech innovations. Nonetheless, I strongly feel that discussing the importance of STEM and its history in the invention of the telephone has allowed people to facilitate human communication. Today, it is no longer necessary for people to be physically close to each other in order to communicate. It is because of the STEM invention of the telephone that people are effortlessly able to conduct meaningful talks at a distance over the telephone, while maintaining reciprocity.