Cleaned manual

README.md

@@ -1,6 +1,6 @@
 # Background
 
-Cell-free fetal DNA fraction is an important estimate during routine NIPT. Its arguably most important role is informing geneticists whether a test is conclusive: if the fraction of fetal-derived fragments is insufficient (this limit has often been debated to be 4%) statements on fetal aneuploidies cannot be made accurately. Furthermore, the fetal fraction carries valuable inherent information on whether observed potential aberrations are fetal-derived. Several techniques exist to deduce this figure, but the far most require additional experimental procedures, which impede routine execution in times of rising NIPT demand. Therefore, we set out to develop PREFACE, a software to accurately predict fetal fraction based on solely shallow-depth whole-genome sequencing data, which is the fundamental base of a default NIPT assay. In contrast to previous efforts, PREFACE enables user-friendly model training with a limited amount of retrospective data, sidelining between-laboratory bias. For sets of roughly 1100 male NIPT samples, a cross-validated correlation of 0.9 between predictions and fetal fractions according to Y chromosomal read counts was noted. The approach enables training with both male and unlabeled female feti. Using our complete cohort (nfemale=2468, nmale=2723), the correlation metric reached 0.94. To date, no shallow-depth whole-genome sequencing based software has been reported to perform better. In addition, PREFACE provides the fetal fraction based on the copy number state of chromosome X. Previously named measures can predict mixed multiple pregnancies and sex chromosomal aneuploidies. All details can be found in PREFACE's [paper](to-be-added-on-acceptance).   
+Cell-free fetal DNA fraction is an important estimate during routine NIPT. Its arguably most important role is informing geneticists whether a test is conclusive: if the fraction of fetal-derived fragments is insufficient (this limit has often been debated to be 4%) statements on fetal aneuploidies cannot be made accurately. Furthermore, the fetal fraction carries valuable inherent information on whether observed potential aberrations are fetal-derived. Several techniques exist to deduce this figure, but the far most require additional experimental procedures, which impede routine execution in times of rising NIPT demand. Therefore, we set out to develop PREFACE, a software to accurately predict fetal fraction based on solely shallow-depth whole-genome sequencing data, which is the fundamental base of a default NIPT assay. In contrast to previous efforts, PREFACE enables user-friendly model training with a limited amount of retrospective data, sidelining between-laboratory bias. For sets of roughly 1100 male NIPT samples, a cross-validated correlation of 0.9 between predictions and fetal fractions according to Y chromosomal read counts was noted (FFY). The approach enables training with both male and unlabeled female feti. Using our complete cohort (nfemale=2468, nmale=2723), the correlation metric reached 0.94. To date, no shallow-depth whole-genome sequencing based software has been reported to perform better. In addition, PREFACE provides the fetal fraction based on the copy number state of chromosome X (FFX). When combined, PREFACE values, FFX and FFY predict mixed multiple pregnancies and sex chromosomal aneuploidies. Details can be found in the corresponding [paper](www.to-be-added-on-acceptance.com).   
 
 # Manual
 
@@ -13,7 +13,7 @@ Each sample (whether it is used for training or for predicting) should be passed
 - Example: ```./examples/infile.bed```  
 - Tab-separated file with at least four columns.  
 - The name of these columns (passed as a header) must be 'chr', 'start', 'end' and 'ratio'.  
-    - The possible values for 'chr' are 1 until 22 and X and Y (upper-case letters).  
+    - The possible values for 'chr' are 1 until 22 and X and Y (uppercase).  
     - 'ratio' corresponds to the log2-transformed ratio between the observed and expected copy number.  
     - Loci can be indeterminable (e.g. at repeats). Here, 'ratio' values should be expressed as 'NaN'.  
 - The order of rows does not matter. Yet, it is of paramount importance that, for a certain line, file x deals with the same locus as file y. This implies, of course, that all copy number alteration files have the same number of lines.