SOP draft for bioinformatics programs, it needs your review and help!

[owen_han]

I am applying for bioinformatics PhD Program this month with extremely limited time to polish my SOP, If you could review my SOP and give me some advice, it will be greatly appreciated.

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Academic Statement of Purpose:
With four years of education at East China University of Science and Technology, several years of dry lab research experiences in both biology and medicine, and great passion in bioinformatics, I am applying to your distinguished PhD program in XXX to further my research skills. 
During my first two years of college, I studied learning and memory mechanisms in nervous systems. My affection for biology and bioinformatics started since then. After reading relevant literature, I realized that mutations in genes could play a critical role in mental misbehavior. To advance my knowledge in this process, I joined Prof. __’s lab for a project studying CDKL3’s function in mental retardation. Through DNA sequence analysis in animal models, I came to know the fascinating fact that some tiny variants in gene could make a huge difference in biological pathways and physiological outcomes. Later, encouraged by Prof. __ to pursue interdisciplinary studies in biology, computer science and medicine, I joined the Laboratory of Molecular Modeling and Design. I worked on a national research project for computational prediction of drug-induced liver toxicity. The basic process is to use machine learning algorithms such as support vector machine (SVM) to produce a drug hepatotoxicity prediction model. The training dataset was derived from literature mining and manually curation. At first, molecular structure was represented by molecular descriptors such as log P and polarizability. The models, however, did not perform well regarding accuracy and AUC values. After reviewing related research works, I started to use molecular fingerprints as an alternative, which would use 0 and 1 to represent sub-structure of molecules. Meanwhile, I kept modifying algorithms’ parameters to get access to the optimal result. After many revisions and verification, my efforts finally paid off. Models using FP4/MACCS fingerprints and SVM algorithm were found to have a good performance with accuracy over 0.75. I made our final presentation and we won the city level one in the National Innovation Training Program.

Prepared with practical data mining skills and fundamental knowledge in medication-related adverse outcomes, I further studied toxicogenomics with the intention to unveil the underlying principle of drug toxicity. I chose organophosphate-induced neurotoxicity as my topic which was widely recognized by generally unknown regarding molecular mechanisms. To address this matter, I tried to identify key targets by integrating drug-gene annotations from The Comparative Toxicogenomics Database (CTD) and The Toxin and Toxin Target Database (T3DB), and gene-disease annotations from Online Mendelian Inheritance in Man (OMIM) and Human Genome Epidemiology Network (HuGE). Annotations from these databases varied in confidence and scales, so I designed rigorous quality control workflow, including Bonferroni adjustments of all p-values. Also, I extended drug-target-disease associations using network-based interference algorithm. The results turned out well. I successfully identified 21 key targets between organophosphates and Parkinson's disease in a pilot study, many of them including CYP2D6 and NFE2L2 are supported by previous experimental researches. Further evaluation is ongoing.

My college research experience in medicine not only taught me that genes were probably the most critical factor in drug’s adverse outcomes, but also inspired me to further explore the diseases of genomics origin. After graduation, I got the opportunity to work on a cancer genomics study conducted by Lemon Data Bio-Tech Company. I joined the research group as an assistant and became a leading role later on. It is believed that cancer is caused by gene mutations. Based on large databases including Catalogue of Somatic Mutations in Cancer (COSMIC) and The Cancer Genome Atlas (TCGA), this study aimed to use statistical methodology to produce functional annotation of somatic variants, which was traditionally done by low-confidence literature mining with limited clinical value. Our comprehensive annotation pipeline could predict active cancer pathways and promising therapeutic drugs for cancer patients based on their SNV profiles. Since dataset is crucial in this workflow, I spent a lot of time discussing with curators in TCGA working group to confirm that our dataset is rigorously chosen and wisely processed. The project goes well and we believe that our model could bring practical values to cancer treatment. Results of this project will be submitted in a few weeks.

“Precision Medicine” has become popular in both research papers and social medias. Behind this modern phrase is a long story of us fighting diseases especially cancer. Since Sidney Farber conducted a pilot clinical trial on children with acute lymphoblastic leukemia, efforts on improving chemotherapy have never stopped. Nowadays, molecular profiling becomes a new way to unlock the complex mechanisms and heterogeneity of cancer. Although our understanding toward cancer is still limited, I strongly believe that exponential growth of genome sequence databases has the promising capacity to let us win the fight with this “incurable” disease, and I am going to give it my best shot. Thus my dedication to a career in bioinformatics is settled. I have unswerving faith to gain more insights about diseases of genomic origin and finally have an actual contribution to clinical practice. Based on my current research, my future plan is detailed below.
1. XXX
2. XXX

Sharing similar interests, University of XXX is an ideal place for my future education and research. I highly admire this distinctive institution with international recognition and respect in both bioinformatics and graduate education. I believe that your innovative interdisciplinary education and training will be the best opportunity to realize my career goal. If granted admission to the XXX program at XXX, I hope to work under Professor XXX, whose … will provide technical framework for my interested research plan. Other faculty members who will prove critical to my proposed project include XXX for his… and …

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Thank you for your time!