Cancer represents a huge challenge in the medical world, necessitating early detection methods to improve treatment outcomes. The field of fragmentomics emerged as a promising option towards developing efficient non-invasive cancer diagnosis tools. By analysing the differences between the cfDNA fragments from blood samples of healthy patients and patients with cancer, this study aims to determine the most important fragmentomics features for cancer detection. The methods present in this work involve extracting features from the cfDNA fragments available in the experimental dataset, applying a pipeline of feature selection techniques that removes the redundant features, training and evaluating a logistic regression and random forest classifiers to differentiate between healthy and diseased samples, and finally extracting the feature weights from the trained models to understand which features contributed the most to the classification task. Filter-based variance thresholding and Correlation-based Feature Selection (CFS) were employed to refine the dataset. Independent t-test and the Mann-Whitney U test are used to calculate the relationship between the cancer and healthy samples. The Pearson correlation coefficient calculates the correlation between each pair of features. The classification performance of the two proposed models is assessed using the train/test split and the nested cross-validation techniques. The evaluation reveals that logistic regression constantly outperforms the random forest and that removing the redundant features increases the performance of both classifiers. Certain genomic bins, mostly on chromosomes 1, 7 and 8, contain significant features for the classification task. These findings suggest that understanding the importance of the fragmentomics features can lead to improved diagnostic tools such as cancer detection based on blood tests.

Detecting cancer at an initial stage could change the course of the disease's development. A non-invasive examination consists of the liquid biopsy of blood, revealing biomarkers that could provide information about the existence of a tumour or not in the organism. The research touches upon the relevance of DNA fragments, precisely the length of fragments, in the detection of cancer. An in-depth interpretation of the fragment length distribution for predicting the state of a patient as being healthy or sick with cancer was approached. The distribution was explored from four perspectives: the complete fragment length distribution, the size range from 90 to 150 bp, important lengths selected by the feature extraction methods and the Fourier Transform of the initial data. These were input in three machine learning models. Using the fragment lengths between 93 and 98 produced accuracy and AUC scores of over 0.85 for all supervised classification models. Processing the data with the Fourier Transform and using the amplitude of spectrums as features in the Random Forest model resulted in an AUC of 0.99.

In recent years, a new way of cancer diagnostics has emerged, the analysis of DNA fragments circulating in the blood of cancer patients known as fragmentomics. This DNA, known as cell-free DNA (cfDNA), is an easily available biomarker for cell types. Deducing the tissue origin of cfDNA can reveal anomalies in cell death caused by diseases. That holds great potential in cancer detection and monitoring. The process of establishing the cell composition of a blood sample is called cell deconvolution. This research paper focuses on the comparison of two methods of cell deconvolution. The first one UXM, solves this problem by employing a reference-based technique using a methylation atlas. The second one reference-free cfSort, utilizes a Deep Learning Neural Network to perform the sample analysis. In the paper, however, a simpler architecture was trained due to the difficulties in reproduction. Experiments have been conducted to assess the sensitivity of both methods. Experiments consisted of 5 major cell types together mixed with white blood cell DNA fragments to assess the sensitivity of each method. Furthermore, different metrics such as Pearson's correlation coefficient have been used to determine the accuracy of both methods. In the end, UXM outperformed cfSort in most metrics, including Pearson's correlation coefficient, indicating its superior accuracy in deconvolution tasks. However, cfSort showed potential for higher prediction accuracy with further development and better documentation. The findings highlight the strengths and limitations of both methods. This study suggests that while UXM is currently more reliable, future improvements in cfSort could make it a viable alternative. Continued research is recommended to enhance the accuracy and transparency of these methods, ensuring their effectiveness in real-world healthcare applications.

Cancer is one of the leading causes of death. To reduce the amount of deaths caused by cancer, a number of different screening methods are used to detect cancer in an earlier stage, to improve sur vival rates when treating patients with cancer. Cur rent screening methods are often invasive, costly and not very accurate. Therefore, new methods are being sought that aim to be cheaper, less in vasive and provide more accurate results. One of these methods is fragmentomics. Multiple methods have been proposed to use fragmentomics analy sis in the context of screening for cancer, includ ing using the short/long ratio as well as investigat ing the nucleotides at the ends of the fragments. Across previous works using fragmentomics anal ysis to predict cancer, different pre-proccessing steps are used, with limited explanation why the pre-processing methods were chosen. Research into the effects of pre-processing steps used when using fragmentomics analysis is lacking. Two main pre-processing steps in the field are correct ing GC-bias and filtering on MAPQ. Here we in vestigated the impact of three GC-correction meth ods by applying the correction method and then analyzing the resulting fragmentation profiles us ing short/long fragment ratios. Furthermore, three different MAPQ filtering thresholds were studied. This showed that Deeptools correction of the GC bias lowered performance, with the accuracy drop ping from 77.8% to 69.4%. Applying LOESS cor rection using all fragments at the same time re sulted in an accuracy of 83.3%, while applying LOESS correction using the short and long frag ments separately resulted in an accuracy of 91.7%. The impact of filtering the data based on mapping quality was determined by comparing the results of analysing all fragments, analyzing only fragments with mapping quality 5, 20 or 30. This showed that not filtering by mapping quality has a big impact on the profiles of cancer samples, with a KS-test statistic of 0.08 for MAPQ 5 and MAPQ 20 and larger differences in correlations between healthy and cancer samples. The performance of classi fication was much higher when not filtering, with an accuracy of 97.3%, which dropped whenever the filtering threshold was raised, bottoming out at 62.7% for a threshold of MAPQ 30. Due to limita tions with the study, the combined pre-processing of not filtering on MAPQ and using the LOESS separate correction were not studied.